DNA and Cell Biology

YY1 -Induced lncRNA PART1 Enhanced Resistance of Ovarian Cancer Cells to Cisplatin by Regulating miR-512-3p/CHRAC1 Axis

Chemoresistance is one of the major obstacles encountered in ovarian cancer (OC) therapy. Long noncoding RNA

A 14-Methylation-Driven Differentially Expressed RNA as a Signature for Overall Survival Prediction in Patients with Uterine Corpus Endometrial Carcinoma

DNA methylation has been implicated as an important mechanism for the development of uterine corpus endometrial carcinoma (UCEC), indicating that methylation-driven genes may be potential biomarkers for survival prediction. In this study, we aimed to identify a new prognostic methylation signature for UCEC based on differentially expressed genes (DEGs) and long noncoding RNAs (lncRNAs) (DELs). Sample-matched RNA-sequencing and methylation-array data were downloaded from The Cancer Genome Atlas database, by analysis of which a total of 269 DEGs and 4 DELs were identified to be methylation driven. Least absolute shrinkage and selection operator analysis screened that 14 methylation-driven genes were significantly associated with overall survival (OS) and thus were used as a signature to establish a prognostic risk model. Based on the median threshold, the patients were divided into the low-risk and the high-risk groups, which showed significantly different survival periods under the Kaplan-Meier curve. The area under receiver operating characteristic curve (AUC) was 0.934, 0.919, and 0.952 for the training, validation, and entire cohort, respectively. Stratification analysis showed that the established risk model may add prognostic values to conventional clinical factors (age, neoplasm histologic grade, and clinical stage). A nomogram was constructed based on the risk model and clinical parameters, with the AUC of 0.978 and c-index of 0.8079. Database for Annotation, Visualization, and Integrated Discovery (DAVID) function enrichment and Human Protein Atlas (HPA) protein expression validation showed 5 of these 14 genes may be especially important for UCEC (hypermethylated lowly expressed:

Prognostic Role of microRNA-205 in Human Gynecological Cancer: A Meta-Analysis of Fourteen Studies

Several studies have revealed that miR-205 plays important roles in the development of gynecological cancers and thus may serve as a potential prognostic biomarker, but the current conclusions remain controversial. Therefore, the goal of this study was to explore the prognostic significance and functional mechanisms of miR-205 based on a meta-analysis and bioinformatics investigation. A total of 14 published studies containing 5835 patients were enrolled by searching the PubMed, EMBASE, and Cochrane library databases, 13 (14 datasets) and 5 (6 datasets) of which evaluated the correlations between the expression level of miR-205 and overall survival (OS) or disease-free survival (DFS)/disease-specific survival (DSS)/progression-free survival (PFS)/distant metastasis-free survival (DMFS), respectively. Furthermore, the use of online Kaplan-Meier plotter database analysis supplemented another seven results for OS. Then, a meta-analysis using these 21 and 6 datasets was performed. As a result, the overall analysis failed to demonstrate any significant associations between miR-205 expression and OS (

Expression of ACAP1 Is Associated with Tumor Immune Infiltration and Clinical Outcome of Ovarian Cancer

ADP-ribosylation factor (Arf) GTPase-activating protein (GAP) with coiled-coil, ankyrin repeat and PH domains 1 (ACAP1) is an Arf6 GAP that regulates membrane trafficking and is critical for the migratory potential of cells. However, the roles of ACAP1 have not been fully explored and its association with clinicopathological features in ovarian cancer is still unknown. In this study, we systematically analyzed multiple databases, including TISIDB, Tumor Immune Estimation Resource (TIMER2.0), Gene Expression Omnibus (GEO), CORTECON, Kaplan-Meier Plotter and LinkedOmics platforms to reveal the clinical significance and function of ACAP1 in ovarian cancer. We found that the expression of ACAP1 was upregulated in ovarian cancer and high ACAP1 expression predicted poor prognosis. Our data demonstrated that the expression and methylation status of ACAP1 were strongly correlated with immune infiltration levels, immunomodulators, and chemokines. Gene set enrichment analysis (GSEA) analysis also showed that the mechanism of ACAP1 in regulating ovarian cancer was related to a variety of immune-related pathways. In addition, we also revealed that the expression of ACAP1 was altered during cell differentiation and associated with cancer cell stemness markers. Our study highlights the clinical significance of ACAP1 in ovarian cancer and provides insight into the novel function of ACAP1 in regulation of tumor immune microenvironment and cancer cell stemness.

Increased Expression of UBE2T Predicting Poor Survival of Epithelial Ovarian Cancer: Based on Comprehensive Analysis of UBE2s , Clinical Samples, and the GEO Database

Ubiquitin-conjugating enzymes E2 (UBE2) have been reported in the microenvironment of various malignant tumors, but their correlation with ovarian cancer (OC) remains elusive. This study aimed to systematically analyze the expression patterns, prognostic value, genetic variation, and biological functions of 12 members of the

m 1 A Regulator TRMT10C Predicts Poorer Survival and Contributes to Malignant Behavior in Gynecological Cancers

N1-methyladenosine (m

Long Noncoding RNA SCAMP1 Targets miR-137/CXCL12 Axis to Boost Cell Invasion and Angiogenesis in Ovarian Cancer

Ovarian cancer (OC) is one of gynecological malignancies that seriously affects women's health. Mounting evidence demonstrated that long noncoding RNAs (lncRNAs), microRNAs (miRNAs), and messenger RNAs (mRNAs) play important roles in various biological processes related to the pathogenesis of OC. This research aimed to investigate the regulatory mechanism of lncRNA SCAMP1/miR-137/CXCL12 (C-X-C motif chemokine ligand 12) axis on OC progression. In this study, we found that SCAMP1 was highly expressed in OC cells, which promoted OC cell invasion and angiogenesis. In addition, our research confirmed that SCAMP1 could bind with miR-137, and SCAMP1 sponged miR-137 to accelerate the progression of OC. We also observed that CXCL12 was a downstream target gene for miR-137, and miR-137 targeted CXCL12 to participate in the regulation of OC. Finally, through TCGA database, we found that SCAMP1 (or CXCL12) was upregulated as well as miR-137 was downregulated in OC tissues, and high (or low) level of them was associated with poor prognosis. miR-137 expression was negatively correlated with SCAMP1 (or CXCL12) expression, and SCAMP1 expression was positively correlated with CXCL12 expression in OC. In summary, our study clarified the role of SCAMP1/miR-137/CXCL12 axis in OC, and this finding may provide a potential therapeutic target of OC.

A microRNA–Messenger RNA Regulatory Network and Its Prognostic Value in Cervical Cancer

Cervical cancer (CC) is the fourth commonest cancer in women worldwide. Increasing evidence proves that microRNA (miRNA)-messenger RNA (mRNA) network is involved in CC. In this study, miRNA and mRNA expression profiles were downloaded from The Cancer Genome Atlas (TCGA) database. Differently expressed miRNAs (DE-miRNAs) and mRNAs (DE-mRNAs) were obtained by "Empirical Analysis of Digital Gene Expression Data in R (EdgeR)" package. Then, functional analyses were conducted. With Cytoscape software, a protein-protein interaction (PPI) network was established to identify hub genes that were used for building an miRNA-hub gene network. Next, a prognostic signature based on hub genes was constructed by Cox regression analysis, and its prognostic value was assessed by a nomogram. Finally, the relationship between immune cell infiltration and the three genes in the prognostic model was investigated by using the CIBERSORT algorithm. We screened out 5096 DE-mRNAs and 114 DE-miRNAs between healthy cervical and CC tissues. Then, 102 target DE-mRNAs of upregulated DE-miRNAs and 150 target DE-mRNAs of downregulated DE-miRNAs were obtained. PPI network demonstrated 20 hub nodes with higher connectivity. DE-mRNAs were mostly enriched in pathways in cancer, cell cycle, and proteoglycans in cancer. The miRNA-hub gene network showed that most hub genes could be potentially modulated by miR-200c-3p, miR-23b-3p, and miR-106b-5p. Quantitative real-time PCR proved that 10 miRNAs were downregulated and 6 mRNAs were upregulated markedly in CC tissues. Furthermore, a prognostic signature was established based on enhancer of zeste homolog 2 (

MALAT1 Inhibits Proliferation of HPV16-Positive Cervical Cancer by Sponging miR-485-5p to Promote Expression of MAT2A

Cervical cancer is the leading cause of morbidity and mortality in women throughout the world, human papillomavirus 16 (HPV16) is the main type of HPV causing invasive cervical cancer. However, the underlying mechanism of the high carcinogenicity of HPV16 remains unclear. In the current study, we documented that metastasis-associated lung adenocarcinoma transcript 1 (

miR-182-5p and miR-96-5p Target PIAS1 and Mediate the Negative Feedback Regulatory Loop between PIAS1 and STAT3 in Endometrial Cancer

The expressions and roles of protein inhibitor of activated STAT (PIAS) proteins, a group of proteins with STAT inhibition and SUMOylation E3 ligase activity, are rarely revealed in endometrial cancer (EC). In this study, we analyzed the expressions of PIASs and their relationships with clinical features by mining online data through web servers, including UALCAN and Gene Expression Profiling Interactive Analysis (GEPIA) in EC. The expressions of PIASs in EC tissues were further validated by immunohistochemistry (IHC). The online analyses revealed only PIAS1 was consistently downregulated both at mRNA and protein level in EC, which was validated by the IHC. Subsequently, the mechanism of PIAS1 downregulation was explored with online tools like UALCAN, cBioPortal, LinkedOmics, and the Encyclopedia of RNA Interactomes (ENCORI). The results indicated that the mutation rate of PIAS1 was extremely low and not associated with PIAS1 expression. The promoter methylation level of PIAS1 was comparable between normal and EC tissues. miR-182-5p and miR-96-5p with negative association with PIAS1 in EC were predicted to target PIAS1. Dual luciferase reporter assay confirmed miR-182-5p and miR-96-5p could target PIAS1 in EC. MiR-182-5p and miR-96-5p inhibitors could upregulate PIAS1 in EC cells. Moreover, ectopic PIAS1 expression and STAT3 inhibitor treatment significantly inhibited STAT3's activity and the levels of miR-182-5p and miR-96-5p in EC cells. Collectively, our findings revealed PIAS1 was downregulated in EC, which was caused by upregulation of miR-182-5p and miR-96-5p, and PIAS1 downregulation further activated STAT3 and increased the expression of miR-182-5p and miR-96-5p, confirming miR-182-5p and miR-96-5p mediated the negative feedback regulatory loop between PIAS1 and STAT3 in EC.

Identification of a Multi-RNA-Type-Based Signature for Recurrence-Free Survival Prediction in Patients with Uterine Corpus Endometrial Carcinoma

Uterine corpus endometrial carcinoma (UCEC) is one of the leading causes of death from gynecological cancer due to the high recurrence rate. A recent study indicated that molecular biomarkers can enhance the recurrence prediction power if they were integrated with clinical information. In this study, we attempted to identify a new multi-RNA-type-based molecular biomarker for predicting the recurrence risk and recurrence-free survival (RFS). Matched mRNA (including lncRNA) and miRNA RNA-sequencing data from 463 UCEC patients (

Histone Lactylation-Driven GPD2 Mediates M2 Macrophage Polarization to Promote Malignant Transformation of Cervical Cancer Progression

Cervical cancer (CC) is the most common cancer in women. This study aims to explore the molecular mechanism of lactate secreted by CC cells modulating macrophage polarization in CC via histone lactylation. Normal cervical epithelium (NCE), low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL), and cervical squamous cell carcinoma (CESC) were collected to assess H3K18la level and macrophage infiltration. Macrophages were incubated with SiHa cell-derived conditioned medium to detect M1 and M2 markers. NCE, HSIL, and CESC samples were used for ChIP-seq of H3K18la. Histone lactylation-dirven

Diagnostics and Therapeutic Potential of miR-205 and miR-34a in Ovarian Cancer Management: A miRNA-Target-Based Analysis

Epithelial ovarian cancer (EOC) treatment strategies mainly focused on surgery combined with chemotherapy. Recent targeted therapy techniques emerge as milestone and could be used for management of ovarian cancer (OC) progression with more efficacy. The aim is to evaluate the therapeutic and diagnostic potential of microRNA (miRNA) in management of EOC using in silico and quantitative real-time PCR (qRT-PCR) expression analysis. We performed functional enrichment and miRNA-Target genes expression analysis in 48 EOC and 22 normal tissue samples using qRT-PCR and correlated with miRNA expression data in matched samples to evaluate the diagnostic and therapeutic potential of miRNA in OC management. In silico functional enrichment analysis revealed miRNA association with disease. Target genes of miRNAs participate in several biologically important pathways leading to cancer progression. Targets of miRNA-205 and miRNA-34a were significantly downregulated, and upregulated, respectively, in EOC. Moreover, significant negative correlation between relative expression of miRNA-205 and target genes (BCL2, ZEB1, E2F1, and TP53) was observed with r  = −0.813; r  = −0.755; r  = −0.559; and r  = −0.767, respectively. Similarly, miRNA-34a also showed higher negative correlation with target genes (MDM4, MAPK3, BRCA1, AREG) with r  = −0.840; r  = −0.870; r  = −0.622; and r  = −0.623, respectively. In addition, receiver operating characteristics analysis of combined miRNA panel, miRNA-205-Target gene panel, and miRNA-34a-Target gene panel exhibited higher diagnostics value with area under the curve (AUC) of 92.7 ( p  < 0.0001), 94.8 ( p  < 0.0001), and 98.3 ( p  < 0.0001), respectively. Negative Correlation between miRNA and target genes expression data in matched samples highlights therapeutic potential of miRNA in EOC management. Moreover, combined diagnostic potential of miRNA-target gene panel could predict risk of EOC with higher AUC, sensitivity, and specificity.

Identification of Key Genes in Association with Progression and Prognosis in Cervical Squamous Cell Carcinoma

Cervical cancer remains a primary cause of female death in developing countries, but its prognosis can be greatly improved if patients are diagnosed earlier. In the present study, we screened the common differentially expressed genes (DEGs) of cervical squamous cell carcinoma (CESC) from dataset GSE7803, Gene Expression Omnibus, and The Cancer Genome Atlas databases. An integrated bioinformatics analysis was performed based on these DEGs for their enrichment in functions and pathways, interaction network, prognostic signature, and candidate molecular drugs. As a result, 164 (114 upregulated and 47 downregulated) DEGs of CESC were identified for further investigation. We then conducted the gene ontology term enrichment and Kyoto Encyclopedia of Genes and Genomes Pathway analyses to reveal the underlying functions and pathways of these DEGs. In the protein-protein interaction network, hub module and hub genes were identified. Five genes of significant prognostic value-

Identification of miRNA-mRNA Regulatory Network and Construction of Prognostic Signature in Cervical Cancer

Cervical cancer (CC) remains a most prevalent female cancer worldwide, but there are few biomarkers used in diagnosis and prognosis of CC. The aim of this study is to find reliable and effective biomarkers regarding CC development. Microarray datasets were downloaded from the Gene Expression Omnibus (GEO) database to search potential miRNA-mRNA in CC. The gene ontology term enrichment and Kyoto encyclopedia of genes and genomes (KEGG) pathway analyses were conducted to reveal the underlying functions and pathways of differently expressed genes (DEGs). Univariate Cox, multivariate Cox, and risk scoring methods were performed to identify a prognostic model. A total of 209 DEGs of CC were identified. In the protein-protein interaction network, hub module, and hub genes were recognized. Based on DEGs, three small molecules (thioguanosine, apigenin, and trichostatin A) were screened out as potential drugs. Two miRNAs (hsa-mir-101-3p and hsa-mir-6507-5p) and some transcription factors were found to be associated with prognosis of CC. A five-candidate gene signature (

The Role of High-Risk Human Papillomavirus-Related Long Non-Coding RNAs in the Prognosis of Cervical Squamous Cell Carcinoma

Cervical cancer (CC) is a malignant tumor that could seriously endanger women's life and health, of which cervical squamous cell carcinoma (CESC) accounts for more than 80%. High-risk human papillomavirus (HR-HPV) infection is the primary cause of CC. The 5-year survival rate is low due to poor prognosis. We need to explore the pathogenesis of CC and seek effective biomarkers to improve prognosis. The purpose of this research is to construct an HR-HPV-related long non-coding RNA (lncRNA) signature for predicting the survival and finding the biomarkers related to CC prognosis. First, we downloaded the CESC data from The Cancer Genome Atlas (TCGA) database to find HR-HPV-related lncRNAs in CC. Then, the differentially expressed lncRNAs were analyzed by univariate and multivariate Cox regression. Six lncRNAs were found to be associated with the prognosis and can be used as independent prognostic factors. Next, based on these prognostic genes, we established a risk score model, which showed that patients with higher score had poorer prognosis and higher mortality. Moreover, the Kaplan-Meier curve of the model indicated that the model was statistically significant (

Identification of MMP1 as a Potential Prognostic Biomarker and Correlating with Immune Infiltrates in Cervical Squamous Cell Carcinoma

Cervical squamous cell carcinoma (CESC) is a human papillomavirus-driven tumor that the underlying molecular mechanisms are unclear. This study aimed to elucidate the key candidate genes and potential mechanism in CESC by bioinformatics analysis. A total of 132 common differentially expressed genes (DEGs) were identified based on three expression profile data sets. A multivariate Cox proportional regression model was used to develop a four-gene prognostic signature. Mechanistically, the correlationship between MMP1 and tumor-infiltrating lymphocytes was further analyzed. Furthermore, annotations were investigated by Gene Ontology (GO) and The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Finally, potential drugs for CESC treatment were predicted by Connectivity Map. We profiled four genes (

QKI-Regulated Alternative Splicing Events in Cervical Cancer: Pivotal Mechanism and Potential Therapeutic Strategy

QKI is a vital regulator in RNA splicing and maturation, but its role in cervical cancer (CC) is little known. In this study, we found that QKI is decreased in human CC, and overexpression of QKI inhibits HeLa cell proliferation and promotes the apoptosis of cancer cells. We identified hundreds of endogenous QKI-regulated alternative splicing events (ASEs) and differentially expressed genes (DEGs) in QKI-overexpressed HeLa cells by RNA-seq and selectively validated their expression by quantitative reverse-transcription polymerase chain reaction. The gene ontology and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis showed that QKI-regulated ASEs and DEGs were closely related to cancer, apoptosis, and transcriptional regulatory functions. In short, QKI may affect the occurrence and development of CC by regulating gene expression through AS.