Journal of Receptors and Signal Transduction

Osthole inhibited cell proliferation and induced cell apoptosis through decreasing CPEB2 expression via up-regulating miR-424 in endometrial carcinoma

Verapamil modulates NFAT2 to inhibit tumor growth and potentiates PD1ab immune checkpoint inhibitor therapy in cervical cancer treatment

Current evidence suggests a high co-prevalence of hypertension and cervical cancer. Accordingly, blood pressure control is indicated during anti-tumor drug therapy in this patient population. Over the past few years, immunotherapy has made great strides in treating different cancers. However, the role and clinical significance of verapamil as a first-line anti-hypertensive drug during immunotherapy remain poorly understood, emphasizing the need for further studies. Murine cervical cancer models were employed to assess the effect of verapamil monotherapy and combination with PD1ab. Immunohistochemistry was conducted to quantify the abundance of CD8+ T cell and Ki67+ cells. Several in-vitro and in-vivo assays were used to study the effects of verapamil and explore the preliminary mechanism. Monotherapy with verapamil or PD1ab immune checkpoint inhibitor significantly suppressed the growth of subcutaneously grafted U14 cells in WT BABL/c mice, respectively, with increased survival time of mice. Consistent results were observed in the melanoma model. Furthermore, we substantiated that verapamil significantly impaired tumor proliferation and migration of SiHa human cervical cancer cells Our results suggest that verapamil inhibits tumor growth by modulating NFAT2 expression and enhancing tumor immune responses to PD1ab, which can be harnessed for cervical cancer therapy, especially for patients with comorbid hypertension. Indeed, further clinical trials are warranted to increase the robustness of our findings.

Overexpression of NDRG2 promotes the therapeutic effect of pazopanib on ovarian cancer

Ovarian cancer is the second commonly seen cancer in the US, patients with ovarian cancer are commonly diagnosed in the advanced stage. Pazopanib is an inhibitor of multiple tyrosine kinases and has been approved in treatment for carcinoma by FDA. N-myc downstream-regulated gene 2 (NDRG2) has been regarded as a cancer suppressor gene and presented an inhibition effect in cancer proliferation, invasion, and migration. The NDRG2 overexpression and inhibition model was firstly constructed in SKOV-3 cells, the apoptotic cells were detected using flow cytometry. The expression of cellular metastasis genes was detected using the qPCR method. The angiogenesis factors was detected using the ELISA method. Expression of each target protein was detected using western blotting analysis. NDRG2 overexpression and inhibition model were constructed in the SKOV-3 cell line, overexpression of NDRG2 enhanced the effect of pazopanib on inhibition of the expression of metastasis-related molecules and angiogenesis-related factors. The apoptosis process of cells was also enhanced after overexpression of NDRG2, and these effects were regulated by the activation of the ASK1/JNK1 signaling pathway. NDRG2 might be a therapeutic target in treatment for ovarian cancer.

Long noncoding RNA LINC00858 promotes the progression of ovarian cancer via regulating the miR-134-5p/TRIM44 axis

Recent studies have shown that many long noncoding RNAs (lncRNAs) are abnormally expressed in ovarian cancer and involved in the pathological progress of ovarian cancer. In the present study, we aimed to investigate the role of lncRNA LINC00858 and the potential mechanism in ovarian cancer. The qRT-PCR was used to measure the expression levels of LINC00858 and miR-134-5p in ovarian cancer tissue specimens and cell lines. Loss-of-function assays were performed to investigate the role of LINC00858 in ovarian cancer. MTT assay was carried out to measure cell proliferation. Transwell assays were performed to determine cell migration and invasion. Biological information analysis and luciferase report gene assay were used to verify potential downstream genes of LINC00858. The xenograft mouse model was established to analyze tumor growth

Investigating the inhibitory potential of natural bioactive compounds against cyclin-dependent kinase 13: virtual high throughput screening and MD simulation studies to target CDK signaling

Long noncoding RNA ROR1-AS1 enhances STC2-mediated cell growth and autophagy in cervical cancer through miR-670-3p

Cervical cancer (CC) ranks the fourth among female malignancies and has become a dominating cause for tumor-associated death nowadays. More and more documents have proposed that long noncoding RNAs (lncRNAs), which emerge as pivotal biomarkers, actively participate in the regulation of human carcinomas. LncRNA ROR1-AS1 is a recently identified RNA that is highlighted for its crucial role in the biological processes of cancers. However, the role and molecular mechanism of ROR1-AS1 in CC have not been clarified yet. In the current study, RT-qPCR analysis uncovered that ROR1-AS1 expression was evidently upregulated in CC tissues and cell lines. Functional experiments (CCK-8, EdU, TUNEL, wound healing and Transwell assays as well as western blot analysis) revealed that knockdown of ROR1-AS1 markedly suppressed the malignant phenotypes of CC cells These data suggested that ROR1-AS1 contributed to the malignant properties of CC cells through sponging miR-670-3p and upregulating of STC2.

Berberine modulates Keratin 17 to inhibit cervical cancer cell viability and metastasis

Berberine (BBR) acts as a tumor suppressor in different cancer cells. Our paper exerted efforts to discover the effect of BBR on cervical cancer. Human cervical cancer cell lines SiHa and Ca Ski were treated with different concentrations of BBR. Cell viability, apoptosis, migration and invasion were detected by MTT assay, flow cytometry, wound healing assay, and Transwell assay, respectively. Expressions of Bcl-2-associated X protein (Bax), Bcl-2, cleaved (C) caspase-3 and epithelial-mesenchymal transition (EMT)-related proteins were measured by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. Keratin 17 (KRT17) expression in cervical cancer was identified by GEPIA2 and qRT-PCR. Rescue assay was then performed to assess the functional interaction between BBR and KRT17. Human cervical cancer cell viability, migration, and invasion were inhibited by BBR. BBR promoted cell apoptosis by increasing Bax and C caspase-3 expressions and decreasing Bcl-2 expression. Besides, BBR inhibited EMT in cells by decreasing the expressions of MMP-9, N-cadherin and Vimentin and increasing E-cadherin expression. Effects of BBR on cervical cancer cells were in a dose-dependent manner. Higher expression of KRT17 was found in cervical cancer SiHa and Ca Ski cells. BBR rescued the effects of KRT17 on promoting cell viability, metastasis, and the expressions of Bcl-2, MMP-9, N-cadherin and Vimentin, and suppressing apoptosis and the expressions of Bax, C-caspase-3 and E-cadherin. BBR inhibited cervical cancer cell viability, metastasis and EMT but promoted cell apoptosis

Isoflurane activates AMP-activated protein kinase to inhibit proliferation, and promote apoptosis and autophagy in cervical carcinoma both in vitro and in vivo

Isoflurane is an extensively used inhalational anesthesia, and its carcinogenic or anti-cancerous effect has been identified recently. However, the specific role of isoflurane in cervical cancer remains unclear. This study aimed to investigate the function of isoflurane in cervical cancer as well as the underlying mechanism. After isoflurane treatment, HeLa cell viability, percentage of apoptotic cells, expression of active caspase-3/9 were examined by CCK-8 assay, Annexin V-FITC/PI double staining, and Western blot analysis, respectively. ROS generation, ratio of NAD Isoflurane inhibited cell viability and induced apoptosis evidenced by upregulation of active caspase-3/9 in HeLa cells. Oxidative stress was triggered by isoflurane, as isoflurane elevated ROS level, and lowered ratio of NAD Isoflurane activated AMPK to inhibit proliferation and promote apoptosis and autophagy both

TMEM48 promotes cell proliferation and invasion in cervical cancer via activation of the Wnt/β-catenin pathway

Transmembrane proteins (TMEMs), spanning the entire width of lipid bilayers and anchored to them permanently, exist in diverse cell types to implement a series of essential physiological functions. Recently, TMEM48, a member of the TMEM family, has been demonstrated to be closely associated with tumorigenesis. However, little is known about the specific role of TMEM48 in cervical cancer (CC). This study aimed to investigate the biological functions of TMEM48 in CC. The CCK-8 assay was performed to detect CC cell proliferation. The wound healing and transwell assays were conducted to measure cell migration and invasion, respectively. The levels of TMEM48, β-catenin, T cell factor 1(TCF1) and axis formation inhibitor 2 (AXIN2) were examined by the western blot analysis. Xenograft models were established for the tumorigenesis assay

Plantamajoside inhibits hypoxia-induced migration and invasion of human cervical cancer cells through the NF-κB and PI3K/akt pathways

Plantamajoside (PMS) is a major compound of Plantago asiatica and possesses anti-tumor property in several types of cancers. However, the effect of PMS on cervical cancer has not been investigated. This study aimed to investigate the effect of PMS on the migration and invasion of cervical cancer cell lines under hypoxic condition. Our results demonstrated that PMS significantly inhibited hypoxia-caused increases in cell migration and invasion of cervical cancer cells. The hypoxia-induced epithelial-mesenchymal transition (EMT) process was prevented by PMS with increased E-cadherin expression, and decreased expression levels of N-cadherin and vimentin in cervical cancer cells. Besides, the expression levels of transcription factors slug and snail were suppressed by PMS in hypoxia-induced cervical cancer cells. The increased mRNA and protein levels of hypoxia-inducible factor 1alpha (HIF-1α) in hypoxia-induced cervical cancer cells were prevented by PMS. Furthermore, PMS blocked the hypoxia-induced activation of NF-κB and PI3K/Akt pathway in cervical cancer cells. Taken together, these findings suggest that PMS exerted an anti-tumor activity in cervical cancer through preventing the hypoxia-induced EMT. Thus, PMS might serve as a therapeutic agent for the treatment of cervical cancer.

LncRNA TDRG1 promotes the proliferation, migration, and invasion of cervical cancer cells by sponging miR-214-5p to target SOX4

The pathogenesis of cervical cancer (CC) at molecular level has attracted much research attention. The current study aimed to explore the effects of LncRNA TDRG1 on cellular process in CC cells and its molecular mechanism. Expressions of TDRG1 and miR-214-5p in CC and normal tissues and CC cells were measured by quantitative real-time polymerase chain reaction (qRT-PCR). The effects of TDRG1, miR-214-5p, and SOX4 on cell proliferation, migration, invasion, and EMT process of CC cells were detected by Cell Counting Kit-8 (CCK-8), colony formation, wound-healing, Transwell, and Western blot assays, respectively. StarBase and Targetscan7.2 were used to predict the target genes of TDRG1 and miR-214-5p, and the predictions were verified by dual-luciferase reporter assay. The expression of SOX4 in CC and normal tissues, and CC cells transfected with siTDRG1 or miR-214-5p inhibitor was determined by qRT-PCR. The results showed that expression of TDRG1 was up-regulated, while that of miR-214-5p was down-regulated in CC. The target genes of TDRG1 and miR-214-5p were verified to be miR-214-5p and SOX4, respectively. Knocking down TDRG1 expression could inhibit cell proliferation, colony, migration, and invasion abilities, and EMT process, whereas the inhibition of miR-214-5p expression partially reversed such results. Moreover, high SOX4 expression was observed in CC tissues, and down-regulating TDRG1 expression reduced the SOX4 expression while down-regulating miR-214-5p expression alleviated such an inhibition. In conclusion, TDRG1 acts as cancer promoter in CC through promoting cell proliferation, migration, invasion, and EMT process to modulate SOX4 expression through adsorbing miR-214-5p.

Estrogen receptors as potential therapeutic target in endometrial cancer

Endometrial cancer (EC) is one of the most common gynecological carcinomas in both developed and developing countries. Majority of the gynecological malignancies are hormonally driven where estrogen signaling acts as an oncogenic signal. Estrogen's effects are mediated