Cell Biochemistry and Biophysics

3-Aminobenzamide-linked Multifunctional Nanoparticles: A Potent Strategy for Modulating PARP1 in Cervical Cancer Cells

Resistance to chemotherapy remains a major obstacle in effective cancer treatment. To address this challenge, we developed multifunctional Fe

Cancer Stem Cell Regulation as a Target of Therapeutic Intervention: Insights into Breast, Cervical and Lung Cancer

Cancer Stem Cells (CSCs) play an important role in the development, resistance, and recurrence of many malignancies. These subpopulations of tumor cells have the potential to self-renew, differentiate, and resist conventional therapy, highlighting their importance in cancer etiology. This review explores the regulatory mechanisms of CSCs in breast, cervical, and lung cancers, highlighting their plasticity, self-renewal, and differentiation capabilities. CD44+/CD24- cells are a known marker for breast CSCs. Markers like as CD133 and ALDH have been discovered in cervical cancer CSCs. Similarly, in lung cancer, CSCs identified by CD44, CD133, and ALDH are linked to aggressive tumor behavior and poor therapy results. The commonalities between these tumors highlight the general necessity of targeting CSCs in treatment efforts. However, the intricacies of CSC activity, such as their interaction with the tumor microenvironment and particular signaling pathways differ between cancer types, demanding specialized methods. Wnt/β-catenin, Notch, and Hedgehog pathways are one of the essential signaling pathways, targeting them, may show ameliorative effects on breast, lung and cervical carcinomas and their respective CSCs. Pre-clinical data suggests targeting specific signaling pathways can eliminate CSCs, but ongoing clinical trials are on utilizing signaling pathway inhibitors in patients. In recent studies it has been reported that CAR T based targeting of specific markers may be used as combination therapy. Ongoing research related to nanobiotechnology can also play a significant role in diagnosis and treatment purpose targeting CSCs, as nanomaterials can be used for precise targeting and identification of CSCs. Further research into the targeting of signaling pathways and its precursors could prove to be right step into directing therapies towards CSCs for cancer therapy.

Harnessing THz Technology: Biosensor for Highly Accurate Cervical Cancer Cell Detection via Refractive Index

In order to rapidly identify various species of cancer cells in the tissues of person, a unique diamond shaped hollow-core photonic crystal fiber (PCF)-formed by optical waveform is developed and computationally studied. In this investigation, we found the most prevalent cancers, such as HeLa-derived cervical carcinoma. Since normal and cancer cells differ in their refractive indices (RIs), other significant optical properties can be assessed using this information. With the use of the finite element method, a computational tool for solving simultaneous equations, the defining characteristics the suggested cancer cell sensor are examined using COMSOL-Multiphysics software. Additionally, strict mesh parts are used to preserve the utmost level of modeling realism. At 2.4 THz, the PCF detector attains a Relative Sensitivity of around 97.51% and 96.29%, Confinement Loss of 6.1 × 10

Association Between Recurrence of High-grade Squamous Intraepithelial Lesions of the Uterine Cervix and p16, C-myc and PIK3CA Proteins—A Single-center Retrospective Study

Cervical high-grade squamous intraepithelial lesions (HSIL) are one of the common types of cervical cancer precancerous changes, and HPV16/18 positivity is a risk factor for HSIL recurrence. By detecting the expression of relevant markers in the lesion tissue of recurrent patients, it is helpful for the diagnosis of HPV16/18 positivity and can provide a basis for disease recurrence risk assessment. Therefore, this study analyzed the relationship between p16, C-myc, PIK3CA proteins and HPV16/18 positivity in recurrent cervical HSIL patients. By examining the p16, C-myc, and PIK3CA proteins in the cervical lesion tissue of 180 HSIL recurrent patients who underwent examination in the hospital from January 2020 to December 2022, this study analyzed the relationship between p16, C-myc, and PIK3CA proteins and HPV16/18 positivity. PIK3CA expression detection found that the proportion of positive expression of p16, C-myc, and PIK3CA in HPV16/18 (+) patients was significantly higher than that in HPV16/18 (-), and the expression of HPV16/18 in HSIL patients was significantly positively correlated with p16, C-myc, and PIK3CA. Meanwhile, a prediction model F was constructed based on binary logistic regression analysis data with good fit, and through ROC curve analysis. It was found that p16, C-myc, PIK3CA, and logistic model F can effectively predict HPV16/18 (+), with model F having the best diagnostic performance.

Study on the Role of EPHB6 in Inhibiting the Malignant Progression of Cervical Cancer C33A Cells by Binding to CBX7

Cervical cancer stands as the most frequently diagnosed malignancy affecting the female reproductive. The erythropoietin-producing hepatocyte (Eph) family tyrosine kinases play important roles in tumorigenesis and cancer aggression. However, the exact role of EPHB6 in cervical cancer remains unknown. The present study investigated the role of EPHB6 in the malignant process of cervical cancer. GEPIA, tnmplot and kmplot database was used to study the expression of EPHB6 in cervical cancer tissues. western blotting was used to detect the expression of EPHB6, CyclinD, CDK4, CDK6, CBX7, MMP2 and MMP9. CCK8 and EDU staining were used to detect cell proliferation. Wound healing and transwell were used to detect cell proliferation and migration. Flow cytometry was used to detect cell cycle level. The linkedomics database was used to predict the correlation of EPHB6 and CBX7 in cervical cancer. Subsequently, HDOCK server was used to predict the combination of EPHB6 and CBX7. Our current results suggested that the expression of EPHB6 is reduced in cervical cancer tissues and cell lines, and the lower the expression, the worse the prognosis. Moreover, overexpression of EPHB6 inhibits cell proliferation, invasion and migration and cycle acceleration of C33A cells. Furthermore, EPHB6 and CBX7 bind to each other in C33A cells, and EPHB6 inhibits cell proliferation, invasion, migration and cell cycle acceleration in cervical cancer by binding to CBX7. EPHB6 expression is reduced in cervical cancer tissues and cells. Its overexpression inhibits proliferation, invasion, migration, and cell cycle acceleration in C33A cells, exhibiting synergy when bound to CBX7.

17β-estradiol Inhibits Oxidative Stress-Induced Apoptosis in Endometrial Cancer Cells by Promoting FOXM1 Expression

The steroid hormone 17β-estradiol (E2) has a significant impact on the development and progression of tumors. E2 stimulates tumor cell growth and metabolism, leading to an increase in reactive oxygen species (ROS) production. However, the rise in ROS levels is not sufficient to cause severe harm to cancer cells. and the mechanisms that regulate ROS are not well understood. Since FOXM1 plays a crucial role in the production of ROS, we aimed to investigate the impact of E2 on oxidative stress and the involvement of FOXM1 in the Ishikawa endometrial cancer cell line. Our research revealed that E2 controls the levels of ROS inside cells and safeguards them from apoptosis by promoting the expression of FOXM1. We observed a decrease in the expression of FOXM1 alongside an increase in oxidative damage. Moreover, cells demonstrated elevated levels of FOXM1 and ERα upon E2 treatment. Overall, our findings suggest that E2 prevents apoptosis induced by oxidative stress in endometrial cancer cells by encouraging the expression of FOXM1, potentially affecting ERα.

CORO1C Regulates the Malignant Biological Behavior of Ovarian Cancer Cells and Modulates the mRNA Expression Profile through the PI3K/AKT Signaling Pathway

Ovarian cancer (OC) is a frequently occurring gynecological tumor, and its global incidence has recently increased. Coronin-like actin-binding protein 1C (CORO1C) is known to activate the phosphoinositide 3-kinase (PI3K)-protein kinase B (AKT) pathway and promote tumor progression. However, its role in OC remains unclear. This study investigated the role of CORO1C in OC malignancy. In this study, quantitative real-time polymerase chain reaction (qRT-PCR) was used to examine AKT and CORO1C mRNA expression in clinical OC tissues and cells. Immunohistochemical analysis and western blotting were used to examine protein expression in OC tissues and cells, respectively. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), scratch wound-healing, and Transwell assays were performed to examine cell proliferation and migration. RNA-Seq was used to validate the relationship between AKT and CORO1C expression. The results showed that CORO1C was highly expressed in clinical OC tissues and SKOV3 cells, correlating with the International Federation of Gynecology and Obstetrics (FIGO) stage. Furthermore, CORO1C knockout inhibited the proliferation, migration, and invasion of SKOV3 cells; altered the gene expression patterns in these cells; and was closely associated with the PI3K/AKT pathway. Western blotting confirmed that CORO1C knockout reduced the levels of phosphorylated PI3K and AKT. Additionally, CORO1C knockout increased phosphatase and tensin homologs deleted on chromosome 10 (PTEN) protein expression, whereas CORO1C overexpression decreased it. In conclusion, this study demonstrated that high CORO1C levels in OC are associated with greater metastasis and worse prognosis. CORO1C negatively regulates PTEN expression, activates the PI3K/AKT pathway, and promotes OC cell malignancy In patients with OC, CORO1C may function as an effective therapeutic and predictive biomarker.

Advancements in Hydrogel-Based Therapies for Ovarian Cancer: A Review

Ovarian cancer, the most deadly gynecologic malignancy, is often resistant to conventional antitumor therapy due to various factors such as severe side effects, unexpected recurrence, and significant tissue damage. The limitations of current treatments and the resistance of invasive tumor cells contribute to these challenges. Hydrogel therapy has recently emerged as a potential treatment option for ovarian cancer, offering advantages such as controllability, biocompatibility, high drug loading capacity, prolonged drug release, and responsiveness to specific stimuli. Hence, the utilization of biodegradable hydrogels as carriers for chemotherapeutic agents has emerged as a significant concern in the field. Injectable hydrogel-based drug delivery systems, in particular, have demonstrated superior efficacy compared to traditional systemic chemotherapy for cancer treatment. The pliability of hydrogel therapy allows for access to anatomical regions that may be challenging for surgical intervention. This review article examines recent advancements in the application of hydrogels for diagnosing and treating ovarian cancer, while also proposing a novel direction for the use of hydrogel technology in this context. The objective of this article is to offer a novel point of reference and serve as a source of inspiration for the advancement of more precise and individualized cancer therapies.

Advances in ovarian tumor stem cells and therapy

Ovarian cancer is considered the most lethal among all gynecological malignancies due to its early metastatic dissemination, extensive spread, and malignant ascites. The current standard of care for advanced ovarian cancer involves a combination of cytoreductive surgery and chemotherapy utilizing platinum-based and taxane-based agents. Although initial treatment yields clinical remission in 70-80% of patients, the majority eventually develop treatment resistance and tumor recurrence. A growing body of evidence indicates the existence of cancer stem cells within diverse solid tumors, including ovarian cancer, which function as a subpopulation to propel tumor growth and disease advancement by means of drug resistance, recurrence, and metastasis. The presence of ovarian cancer stem cells is widely considered to be a significant contributor to the unfavorable clinical outcomes observed in patients with ovarian cancer, as they play a crucial role in mediating chemotherapy resistance, recurrence, and metastasis. Ovarian cancer stem cells possess the capacity to reassemble within the entirety of the tumor following conventional treatment, thereby instigating the recurrence of ovarian cancer and inducing resistance to treatment. Consequently, the creation of therapeutic approaches aimed at eliminating ovarian cancer stem cells holds great potential for the management of ovarian cancer. These cells are regarded as one of the most auspicious targets and mechanisms for the treatment of ovarian cancer. There is a pressing need for a comprehensive comprehension of the fundamental mechanisms of ovarian cancer's recurrence, metastasis, and drug resistance, alongside the development of effective strategies to overcome chemoresistance, metastasis, and recurrence. The implementation of cancer stem cell therapies may potentially augment the tumor cells' sensitivity to existing chemotherapy protocols, thereby mitigating the risks of tumor metastasis and recurrence, and ultimately improving the survival rates of ovarian cancer patients.

Targeted design of green carbon dot-CA-125 aptamer conjugate for the fluorescence imaging of ovarian cancer cell

Aptamer-Carbon Dot (CD) bioconjugation is an attractive target-tracking strategy in detecting cell surface antigens. This study describes an effective imaging paradigm for CA-125 antigen imaging. Our experience encompasses green CD synthesis and characterization, CD-capture probe conjugation through covalent bonding, the hybridization linkage of CD-probe to aptamer and their coupling confirmation, and fluorescent targeted imaging of ovarian cancer cells. As a result, the synthesized CDs from lemon extract by hydrothermal reaction show average size of 2 nm with maximum fluorescence intensity at excitation/emission 360/450 nm. CD-probe construction was provided by functional group interactions of CD and probe via EDC/NHS chemistry. The linkage of CD-probe to aptamer was conducted by Watson-Crick nucleotide pairing. The assessment of CD-probe and CD-probe-aptamer fabrication was validated by the increase in surface roughness through AFM analysis, the diminish of fluorescence intensity of CD after bioconjugation, and particle size growth of the construct. Conjugates with negligible cytotoxicity, appropriate zeta potential, and good aptamer release were applied in cellular imaging. This targeted diagnosis method was employed the four reported DNA aptamers toward fluorescence intensity. The DOV-3 aptamer showed more qualified detection over other aptamer conjugates during fluorescent microscopy analysis. In conclusion, the CD-probe-aptamer conjugate applications as toxic-free method can open new horizons in fluorescent nano-imaging in the field of targeted cancer cell diagnosis.

The Effect of Blocking Neurokinin-1 Receptor by Aprepitant on the Inflammatory and Apoptosis Pathways in Human Ovarian Cancer Cells

Ovarian cancer is the seventh most common cancer globally, and the second most common cancer among women with significant mortality. Toward this end, it is shown that substance P (SP) is involved in tumor initiation and progression through the neurokinin-1 receptor (NK1R). However, the exact molecular mechanism of the SP/NK1R system in ovarian cancer is not yet fully clarified. In this in vitro study, we decided to investigate the effect of the SP/NK1R system and blockage of NK1R by its specific antagonist (Aprepitant) on the proliferation of ovarian cancer cells as well as the alteration of inflammatory pathways. Our results revealed that Aprepitant stimulated apoptotic cell death and attenuated inflammation of ovarian cancer cells through the NF-kB and P53 signaling pathways. After treatment with Aprepitant, the expression of downstream anti-apoptotic genes related to the NF-kB pathway (survivine and bcl2) was decreased. However, we indicated the positive effect of SP on the proliferation of ovarian cancer cells by inducing the expression of NF-kB protein and NF-kB anti-apoptotic target genes. Moreover, Pro-apoptotic p53 target genes (P21 and Bax) were increased through aprepitant treatment, while SP attenuated these genes' expression. Besides, ROS generation in ovarian cancer cells after treatment with SP induced, while blocking of NK1R with Aprepitant reduced the level of ROS generation. Given this, our data suggest that this NK1R might be used as an important therapeutic target in ovarian cancer and Aprepitant could be considered a new drug in ovarian cancer therapy.

Downregulation of N-myc Interactor Promotes Cervical Cancer Cells Growth by Activating Stat3 Signaling

N-myc interactor (NMI), a member of the oncogene Myc family, has been reported to be closely related to the development of cancer. However, the character of NMI in cervical carcinoma has not been reported. Herein, we found that downregulation of NMI protein not only promoted the proliferation, migration, and invasion of HeLa cells, but also decreased their expression of Caspase-3 and Caspase-9. Silencing NMI promotes the epithelial-mesenchymal transition of human cervical carcinoma HeLa cells by upregulating N-cadherin, vimentin, and downregulating E-cadherin. Further investigation illustrated the downregulation of NMI can activate the STAT3 signaling pathway. In conclusion, we found that the downregulation of NMI plays an important role in the progression of cervical cancer, and may served as a novel therapeutic target for cervical cancer.

Targeting HSP90 in Gynecologic Cancer: Molecular Mechanisms and Therapeutic Approaches

Molecular Regulator Driving Endometriosis Towards Endometrial Cancer: A Multi-Scale Computational Investigation to Repurpose Anti-Cancer drugs

Endometriosis is a gynecological disorder among reproductive-aged women. Recent epidemiological investigations suggest endometriosis increases the risk of endometrial cancer. However, the molecular entity leading to endometriosis-to-endometrial cancer is largely unknown. This study aimed to combine a variety of computational approaches to identify the key therapeutic target promoting endometriosis-to-endometrial cancer and screen potential inhibitors against target to prevent cancer development. Our systematic investigations, includes transcriptomic profiling, protein network, pharmacophore modeling, docking, binding free energy calculation, dynamics simulation, and quantum mechanics. The gene expression analysis on endometriosis and endometrial cancer was performed and showed 108 shared upregulated genes in both conditions. Further construction of interaction network with 108 genes showed intercellular adhesion molecule 1 (ICAM1) to be a crucial molecule with a high degree of connectivity that influences vital mechanisms related to cancer pathways. We then generated ligand-based pharmacophore models using established ICAM1 inhibitors. Among the models, the ADRRR_8 pharmacophore exhibited a robust area under curve (AUC = 0.83), was employed to screen 1739 anti-cancer drugs. On screening, 421 anti-cancer drugs displayed ICAM1-inhibiting pharmacophore features. Further, the docking of 421 drugs with ICAM1 showed lanreotide (-7.80 kcal/mol) with better affinity than the reference ICAM1 inhibitor (-3.59 kcal/mol). Further validation though binding free energy and dynamics simulation of the lanreotide-ICAM1 complex showed a high binding affinity of -55.90 kcal/mol and contributed stable confirmation. According to quantum chemical calculations, lanreotide's electronic properties favour ICAM1 binding with highest occupied molecular orbital was -6.91 eV and lowest unoccupied molecular orbital was -3.93 eV. Our study supports using lanreotide to treat endometriosis, which could delay or prevent endometrial cancer. These predictions need to be confirmed and examined to determine the use of lanreotide in endometriosis treatment.

‘Investigation of miRNAs That Affect the PI3K/AKT/mTOR Signaling Pathway in Endometrial Cancer’

Endometrial cancer is a prevalent type of cancer among women worldwide. The irregularity of the PI3K/AKT/mTOR signaling pathway plays a role in the pathogenesis of many cancer types. MicroRNAs are small noncoding RNAs that play crucial roles in the pathogenesis of different cancer types. MicroRNAs target many key components of the PI3K/AKT/mTOR pathway in human tumors. In this study the PI3K/AKT/mTOR pathway was affected in endometrial cancer, and the expression levels of miR-7, miR-17, miR-145, miR-155, miR-206, miR-221, miR-222 were determined. In addition, in silico analyses were examine the molecular interactions between miRNAs and target genes. Identifying dysregulated miRNA expression in endometrial cancer is important for developing miRNA-based therapeutic strategies. In our study, Grade 1 (n = 16), Grade 2 (n = 16), Grade 3 (n = 16), tissues diagnosed with endometrioid adeno carcinoma, control 1 (n = 16) secretory phase and control 2 (n = 16) proliferative phase healthy endometrial tissues without endometrial cancer were included. miRNA expression analysis was performed using the real-time PCR. In our study, the expression of miR-7-5p, miR-145-5p, and miR-206 decreased, whereas the expression of miR-17-5p, miR-221-3p, and miR-222-3p increased in endometrial cancer (p < 0,05). Statistically significant results were not obtained to for the expression levels of miR-21-5p and miR-155-5p. miR-7-5p targets PIK3CD, PIK3R3, PIK3CB and AKT3, miR-17-5p targets PIK3R1 and AKT3, miR-21-5p target PIK3R1, miR-145-5p target AKT3, miR-155-5p targets PIK3CA and PIK3R1, miR-206 target PIK3C2A, miR-221-3p and miR-222-3p target PIK3R1 as identified via in silico analysis. These results can shed light on the development of molecular-targeted therapy strategies. Treatment strategies can be developed by designing ASOs, LNAs, miRNA antagomirs, or miRNA sponges for upregulated miR-17-5p, miR-221-3p, and miR-222-3p, and miRNA mimics for downregulated miR-7-5p, miR-145-5p, and miR-206.

XTP8 Promotes Ovarian Cancer Progression by Activating AKT/AMPK/mTOR Pathway to Regulate EMT

AbstractOvarian cancer (OC) ranks as the fifth leading cause of cancer-related death in women. The main contributors to the poor prognosis of ovarian cancer are the high rates of recurrence and metastasis. Studies have indicated a crucial role for hepatitis B virus X Ag-Transactivated Protein 8 (XTP8), a protein containing the DEP domain, in various cellular processes, including cell growth, movement, and differentiation, across several types of cancers. However, the role of XTP8 in ovarian cancer remains unclear. We observed elevated expression of XTP8 in ovarian cancer. Silencing XTP8 inhibited cell proliferation, promoted apoptosis, and yielded contrasting results in cells overexpressing XTP8. Furthermore, XTP8 facilitated ovarian cancer invasion and migration, triggering epithelial-mesenchymal transition (EMT). Mechanistically, XTP8 silencing led to reduced phosphorylation levels of AKT, increased p-AMPK levels, and decreased p-mTOR levels, while XTP8 overexpression exerted the opposite effects. Additionally, the activation of p-AMPK rescued the promoting effect of XTP8 on EMT in ovarian cancer cell lines, indicating that XTP8 acts as an oncogene by modulating the AKT/AMPK/mTOR pathway. Through transcriptome sequencing to identify downstream targets of XTP8, we found that XTP8 influences the expression of Caldesmon (CALD1) at both transcriptional and translational levels. CALD1 can be considered a downstream target of XTP8. The collaborative action of XTP8 and CALD1 activates the AKT/AMPK/mTOR pathway, regulating EMT to promote ovarian cancer progression. Inhibiting this signaling axis might represent a potential therapeutic target for ovarian cancer.

Cell-Cycle-related Protein Centromere Protein F Deficiency Inhibits Cervical Cancer Cell Growth by Inducing Ferroptosis Via Nrf2 Inactivation

AbstractCervical cancer (CC) is one of the severe cancers that pose a threat to women’s health and result in death. CENPF, the centromere protein F, plays a crucial role in mitosis by regulating numerous cellular processes, such as chromosome segregation during mitosis. According to bioinformatics research, CENPF serves as a master regulator that is upregulated and activated in cervical cancer. Nevertheless, the precise biological mechanism that CENPF operates in CC remains unclear. The aim of this study was to analyze the function of CENPF on cervical cancer and its mechanism. We conducted immunohistochemistry and western blot analysis to examine the expression levels of CENPF in both cervical cancer tissues and cells. To explore the hidden biological function of CENPF in cell lines derived from CC, we applied lentivirus transfection to reduce CENPF manifestation. CENPF’s main role is to regulate ferroptosis which was assessed by analyzing Reactive Oxygen Species (ROS), malonaldehyde (MDA), etc. The vitro findings were further validated through a subcutaneous tumorigenic nude mouse model. Our research finding indicates that there is an apparent upregulation of CENPF in not merely tumor tissues but also cell lines in the carcinomas of the cervix. In vitro and vivo experimental investigations have demonstrated that the suppression of CENPF can impede cellular multiplication, migration, and invasion while inducing ferroptosis. The ferroptosis induced by CENPF inhibition in cervical cancer cell lines is likely mediated through the Nrf2/HO-1 pathway. The data herein come up with the opinion that CENPF may have a crucial role in influencing anti-cervical cancer effects by inducing ferroptosis via the triggering of the Nrf2/HO-1 signaling pathway.

Deciphering Biophysical Modulation in Ovarian Cancer Cells

It has been long known that the oncogenic extracellular environment plays an indispensable role in developing and nurturing cancer cell progression and in resistance to standard treatments. However, by how much the biophysical components of tumour extracellular environment contribute to these processes is uncertain. In particular, the topographic environment is scarcely explored. The biophysical modulation of cell behaviour is primarily facilitated through mechanotransduction-associated mechanisms, including focal adhesion and Rho/ROCK signalling. Dysregulation of these pathways is commonly observed in ovarian cancer and, therefore, biophysical modulation of these mechanisms may be of great importance to ovarian cancer development and progression. In this work, aspects of the biophysical environment were explored using a bioimprinting technique. The study showed that topography-mediated substrate sensing delayed cell attachment, however, cell-cell interactions overrode the effect of topography in some cell lines, such as OVCAR-5. Also, 3D topographical cues were shown to modulate the inhibition of focal adhesion and Rho signalling, which resulted in higher MAPK activity in cells on the bioimprints. It was revealed that c-Src is vital to the biophysical modulation of cell proliferation and inhibition of c-Src could downregulate biophysically modulated MAPK activity. This study provides evidence that the biophysical extracellular environment affects key intracellular mechanisms associated with tumourigenicity in ovarian cancer cells.

HuR Promotes Ovarian Cancer Cell Proliferation by Regulating TIMM44 mRNA Stability

The human antigen R (HuR) could play an essential role in stabilizing the mRNAs of many tumor-associated genes. Little research is performed to investigate the relevant mechanism mediated by HuR to promote the progress of ovarian cancer. The Cancer Genome Atlas (TCGA) dataset was retrieved to calculate the correlation between HuR and translocase of inner mitochondrial membrane 44 (TIMM44) expression. HuR expression plasmid, TIMM44 expression plasmid, siRNA HuR, and TIMM44 siRNAs were further transfected into A2780 and SKOV3 cells. The 3'UTR of TIMM44 fragment was cloned into the back of Renilla luciferase in the pSicheck2 dual fluorescent reporter to indicate the interaction between HuR and TIMM44. Cell count and MTT assay were performed to assay the proliferation ability of A2780 and SKOV3 cells. High-level HuR expression in 56 ovarian cancer patients recruited in Zibo Central Hospital was positively correlated with metastasis status and poor prognosis revealed by Kaplan-Meier analysis. Both HuR and TIMM44 can promote the proliferation of SKOV3 and A2780 cells. A high correlation of HuR and TIMM44 expression was testified in the TCGA data. Luciferase reporter assay confirmed that HuR could bind to TIMM44 to maintain the mRNA stability. TIMM44 siRNA administration inhibited the proliferation of SKOV3 cells, which could not be rescued. All of these indicate that the main function of HuR on ovarian cancer proliferation is mediated by TIMM44 through mRNA stability regulation, and HuR/TIMM44 complex can be used as a target to inhibit the proliferation of ovarian cancer cells.

MicroRNA-625-5p Sponges lncRNA MALAT1 to Inhibit Cervical Carcinoma Cell Growth by Suppressing NF-κB Signaling

The exact expression profile and potential involvement of miR-625-5p in the tumor biology of cervical carcinoma are still elusive. In this study, we aimed to analyze the expression status and possible involvements of miR-625-5p in both clinical tissue samples and cell culture of cervical carcinoma. The relative expression levels of miR-625-5p and NF-κB transcript were determined by real-time polymerase chain reaction. Cell proliferation was measured using Cell Counting Kit-8. The protein levels of Cyclin D1, CDK4, NF-κB, and GAPDH were examined by Western blotting. The regulatory effects of miR-625-5p on NF-κB and MALAT1 were interrogated by luciferase reporter assay. We demonstrated that miR-625-5p was downregulated and predicted better survival in cervical carcinoma. Ectopic over-expression of miR-625-5p inhibited cell growth via targeting NF-κB. We further identified MALAT1 as the competitive endogenous long non-coding RNA for miR-625-5p, and over-expression of MALAT1 attenuated the inhibitory effect of miR-625-5p on NF-κB signaling in cervical carcinoma. Our study characterized the suppressive expression of miR-625-5p in cervical carcinoma and unraveled the importance of MALAT1/miR-625-5p/NF-κB signaling in this disease.

Molecular Mechanism of Cynodon dactylon Phytosterols Targeting MAPK3 and PARP1 to Combat Epithelial Ovarian Cancer: A Multifaceted Computational Approach

Epithelial Ovarian Cancer (EOC) presents a global health concern, necessitating the development of innovative therapeutic strategies to combat its impact. This study was employed to investigate the unexplored therapeutic efficacy of Cynodon dactylon phytochemicals against EOC using a multifaceted computational approach. A total of 19 out of 89 rigorously curated phytochemicals were assessed as potential drug targets via ADMET profiling, while protein-protein interaction analysis scrutinized the top 20 hub genes among 264 disease targets, revealing their involvement in cancer-related pathways and underscoring their significance in EOC pathogenesis. In molecular docking, Stigmasterol acetate showed the highest binding affinity (-10.9 kcal/mol) with Poly [ADP-ribose] polymerase-1 (PDB: 1UK1), while Arundoin and Beta-Sitosterol exhibited strong affinities (-10.4 kcal/mol and -10.1 kcal/mol, respectively); additionally, Beta-Sitosterol interacting with Mitogen-activated protein kinase 3 (PDB: 4QTB) showed a binding affinity of -10.1 kcal/mol, forming 2 hydrogen bonds and a total of 10 bonds with 10 residues. Molecular dynamics simulations exhibited the significant structural stability of the Beta-Sitosterol-4QTB complex with superior binding free energy (-36.61 kcal/mol) among the three complexes. This study identified C. dactylon phytosterols, particularly Beta-Sitosterol, as effective in targeting MAPK3 and PARP1 to combat EOC, laying the groundwork for further experimental validation and drug development efforts.

The Role of Long Non-Coding RNF144A-AS1 in Cancer Progression

Effects of Metformin Treatment Against Endometrial Cancer Cells Cultured In Vitro or Grafted into Female Balb/C Nude Mice: Insights into Cell Response and IGF-1R and PI3K/AKT/mTOR Signaling Pathways

Obesity and type II diabetes are independent risk factors for Endometrial cancer (EC) development. Elevated levels of insulin-like growth factor-1 (IGF-1), insulin resistance, and the increased activity of IGF-1 receptor is linked to EC development through the PI3K/AKT/mTOR pathway. The antidiabetic agent metformin is a promising repurposing drug for cancer treatment, but the mechanisms underlying its effects are not completely known. This study evaluated how metformin could act against the EC cell line Ishikawa cultured in vitro or grafted into female Balb/C nude mice. In vitro experiments demonstrated that treatment with 25 mM of metformin reduced cell viability through promoting cytotoxicity, mitochondrial dysfunction, apoptosis, and cell cycle arrest (G1 phase). Mice treatment with 250 mg/kg of metformin for 28 days did not change serum IGF-1 levels nor decreased the grafted cell-induced tumor weight and cell proliferation, but prevented its volume growth while genes of the IGF1-R and PI3K/AKT/mTOR pathways (AKT2, GAPDH, FOXO3, IGF1R, INSR, MAPK3, MTOR, and SHC1) were downregulated. Metformin treatment was more impacting for the in vitro model, but our molecular results provide valuable insights into the possible action of metformin against EC tumoral cells at physiological level. In-silico analysis using Cytoscape indicated that metformin was not described as interacting with AKT2 and SHC1 proteins. Besides interacting with metformin, mTOR and MAPK3 present the larger number of interactions with the other proteins. These four genes/proteins emerge as potential targets for deepening studies to determine the metformin's role in longer EC treatment using animal models.

TUFT1 Modulates Cell Proliferation, Migration, Invasion, Stemness and EGFR Signaling in Cervical Cancer through Interacting with and Targeting ATF1

Cervical cancer remains a frequently-occurring gynecologic health problem posing a great threat to women. Tuftelin1 (TUFT1), an acidic protein possessing secretory capacity, has been reported to drive cisplatin resistance in cervical cancer cells. Accordingly, the current study is intended to figure out the specific impacts of TUFT1 on the aggressive behaviors of cervical cancer cells and make an in-depth study into the related regulatory mechanism. Firstly, analysis of TUFT1 expression in cervical cancer cells was performed by RT-qPCR and Western blotting. Cervical cancer cell proliferation was estimated via CCK-8 and colony formation assays. Wound healing, transwell as well as sphere formation assays were used to appraise cell migration, invasion, and stemness, respectively. Western blotting examined the expressions of metastasis- and stemness-associated factors and RT-qPCR also tested the expressions of stemness-associated factors. Co-IP assay was used to verify the binding between TUFT1 and activating transcription factor 1 (ATF1). Subsequent ATF1 expression was examined by RT-qPCR and Western blotting after TUFT1 was silenced. After co-transfected with TUFT1 interference and ATF1 overexpression plasmids, aforementioned functional experiments were conducted again. Western blotting also analyzed the expressions of epidermal growth factor receptor (EGFR) signaling-associated proteins. The experimental data determined that TUFT1 expression was fortified in cervical cancer cells and TUFT1 absence diminished cervical cancer cell proliferation, migration, invasion, and stemness. Besides, TUFT1 bond to ATF1 and positively modulated ATF1 expression. Moreover, ATF1 elevation countervailed the impacts of TUFT1 insufficiency on the proliferation, migration, invasion, stemness as well as EGFR signaling in cervical cancer cells. Anyway, TUFT1 might interact with ATF1 to elicit pro-proliferation, pro-metastasis, and pro-stemness properties and inactivate EGFR signaling in cervical cancer, supporting that TUFT1 might be valued as a potential hallmark for cervical cancer.

Innovative Refractive Index Sensor Utilizing Terahertz Spectrum for Early Cancer Detection: a Photonic Crystal Fiber Approach

In this article, we have presented a new cancer sensor with a square core Photonic Crystal Fiber (PCF) to detect the cancerous tissues of the cervix, breast, and skin. This process is thus streamlined and separated by PCF due to its excellent detection characteristics. All required configurations using the finite element method are developed, and various performances of the model are studied using MATLAB. The results depict a mathematical analysis regarding the effectiveness of the sensor within the frequency range of 1.0-2.8 THz. Its relative sensitivity becomes around 99.85% at 2.2 THz with 8.49 × 10

T-Box Transcription Factor 2 Mediates Chemoresistance of Endometrial Cancer via Regulating FSP1-involved Ferroptosis

Chemotherapy is increasingly being used in the first-line treatment of endometrial cancer (EC) patients. However, chemoresistance seriously affects its efficacy. Understanding the underlying molecular mechanisms is critical for EC treatment. We explored the regulatory role of T-Box transcription factor 2 (TBX2)-ferroptosis suppressor protein 1 (FSP1) axis in ferroptosis and chemoresistance of EC. Cisplatin-resistant cell line Ishikawa/DDP cells were utilized to generate TBX2 and FSP1 overexpression and knockdown stable cell lines by using lentivirus infection and puromycin selection. Cell viability and ferroptosis status were evaluated in EC cells with or without Cisplatin and/or FSP1 inhibitor (iFSP1) using CKK-8, lipid peroxidation, malondialdehyde, and lactate dehydrogenase release assays. Endometrial carcinoma xenograft mouse model was established to further explore the function of TBX2-FSP1 axis on ferroptosis and tumor progression in EC. TBX2 suppressed Cisplatin-induced ferroptosis through up-regulating FSP1 expression level in EC cells. On the contrary, knockdown of TBX2 reduced FSP1 expression and significantly promoted Cisplatin-induced ferroptosis. TBX2 or FSP1 overexpression and knockdown promote and inhibit EC tumor growth under Cisplatin treatment, respectively. Interestingly, silence FSP1 could reverse TBX2-mediated ferroptosis inhibition and tumor-promoting effect. TBX2-FSP1 axis inhibits ferroptosis and enhances the Cisplatin resistance, which will provide an important theoretical basis and potential solution for the clinical treatment of EC.

miRNAs that regulate apoptosis in breast cancer and cervical cancer

In today's world, one of the main problems is cancer, which still has a long way to go to cure it, and it brings a lot of financial and emotional costs to the people of society and governments. Breast cancer (BC) and cervical cancer (CC), two of the most common cancers, are caused by several genetic and environmental factors in women. These two cancers' involvement rate is higher than other cancers in women. microRNAs (miRNAs) are non-coding RNA molecules with a length of 18 to 24 nucleotides, which play an important role in post-translational changes. miRNAs themselves are divided into two categories, oncomiRs and tumor suppressors. OncomiRs have a part in tumor expansion and tumor suppressors prevent tumor development and progress. miRNAs can control cellular processes by regulating various pathways including autophagy, apoptosis, and signaling. Apoptosis is a type of programmed cell death that includes intrinsic and extrinsic pathways and is different from other cell death pathways such as necrosis and ferroptosis. Apoptosis controls the growth, differentiation, and death of cells by regulating the death of damaged and old cells, and since miRNAs are one of the factors that regulate apoptosis, and divided into two categories: pro-apoptotic and anti-apoptotic. We decided in this study to investigate the relationship between miRNAs and apoptosis in the most common women's cancers, BC and CC.