Identifying Key Epigenetic Modification-Related Genes for Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma and Cellular Validation.

Disulfidptosis is a new type of regulatory cell death (RCD), but the pathophysiological functions and mechanisms of DRGs in CESC remain to be examined. This study explored the mutation status of disulfidptosis-related genes (DRGs) in cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC). After analyzing the mutation profiles of DRGs in CESC, this study established a prognostic model for CESC and also explored the differences in immune infiltration (accumulation of immune system cells in tissues or organs), related enriched pathways, and drug sensitivity between high-risk and low-risk CESC groups. The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) were accessed to source related data. The mutation profiles of DRGs in CESC were analyzed using Mutect2 software, and disulfidptosis scores were calculated by ssGSEA. WGCNA was performed to identify modular genes, which were further filtered and used to formulate a risk model by applying the survival and glmnet packages. Low- and high-risk groups of CESC patients were classified using the survminer package. GSEA was performed to conduct pathway analysis, and immune infiltration was assessed using the MCPcounter package, ESTIMATE, and TIMER algorithms. Finally, immunotherapy response and drug sensitivity were analyzed using the TIDE method and the pRRophetic package, respectively. Except for NDUFA11, ARL6IP5, EPM2AIP1, GBE1, RBM38, ULK4, and ZBTB47 were found to be the DRGs significantly mutated in CESC. The six genes were integrated to develop a RiskScore model with a relatively high Area Under the Curve (AUC) value. Significant differences between the two risk groups were determined, indicating that the model was highly reliable. Notably, the low-risk group was enriched in energy metabolism-correlated pathways, while the high-risk group was primarily enriched in immune-correlated pathways. The high-risk group showed higher immune cell activity, higher TIDE score, and more B cells than the low-risk group. Drug sensitivity study revealed that the high-risk group was more sensitive to chemotherapy drugs. This study provides novel insights into CESC prognosis, immunotherapy, and drug development, contributing to the clinical treatment for CESC.

The role of Zinc Finger Protein 695 (ZNF695) is unclear in cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC). The objective of this study was to conduct a comprehensive analysis and experimental validation of ZNF695 in CESC. The study investigated the expression of ZNF695 in both pan-cancer and CESC, utilizing data from The Cancer Genome Atlas (TCGA) database to assess its diagnostic value. The present study investigated the association between ZNF695 expression levels and clinical characteristics, as well as prognosis, in patients with CESC. The study explored potential regulatory networks involving ZNF695, including its association with immune infiltration, immune score, stemness index based on mRNA expression (mRNAsi), and drug sensitivity in CESC. We explored the expression of ZNF695 in CESC single cells. ZNF695 expression was validated using GSE29570. ZNF695 was found to be aberrantly expressed in pan-cancer and CESC. There was a significant correlation observed between an elevated level of ZNF695 expression in patients with CESC and histological grade (p = 0.017). Furthermore, a strong association was found between high ZNF695 expression in CESC patients and poorer overall survival (OS) (HR: 1.87; 95% CI: 1.17-3.00; p = 0.009), Progression-free Survival (PFS) (HR: 1.86; 95% CI: 1.16-2.98; p = 0.010), and Disease-specific Survival (DSS) (HR: 1.98; 95% CI: 1.15-3.42; p = 0.014). The expression of ZNF695 in CESC patients (p = 0.006) was identified as an independent prognostic determinant. ZNF695 was associated with steroid hormone biosynthesis, oxidative phosphorylation, and so on. ZNF695 expression correlated with immune infiltration, immune score, and mRNAsi in CESC. ZNF695 expression significantly and negatively correlated with AICA ribonucleotide, BIX02189, QL-XI-92, STF-62247, and SNX-2112 in CESC. ZNF695 gene was upregulated in CESC tissues and cell lines. ZNF695 was significantly upregulated in the CESC cell lines. ZNF695 may be a potential prognostic biomarker and immunotherapeutic target for CESC patients.

The mortality caused by cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) ranks second among female malignant tumour deaths, but their diagnostic and therapeutic targets are still limited. N6-methyladenosine (m6A) is the most common and extensive modification in mRNA molecules, and its methylation regulators participate in regulating the occurrence and development of many tumours. However, whether m6A RNA methylation regulators can be used as independent prognostic indicators of CESC remains unknown. This study unveiled differential expression of 20 m6A RNA methylation regulators between normal and CESC tumour samples, which RNA sequence data and clinical information were obtained from TCGA database. As a result, five m6A RNA methylation regulators (FTO, HNRNPA2B1, RBM15, IGF2BP1, IGF2BP3) were identified to be significantly linked to CESC tumour status. After Lasso cox regression analysis, six m6A RNA methylation regulators (YTHDC2, YTHDC1, ALKBH5, ZC3H13, RBMX, YTHDF1) were chosen to construct a risk signature. CESC patients were then classified as high-risk and low-risk group based on the median risk score. The overall survival (OS) of the CESC patients in high-risk group was significantly lower than that in low-risk group, and the area under curve (AUC) is 0.718. Moreover, the risk model can be an independent prognosis factors for CESC patients and can predict OS of CESC patients with different clinical factors. In conclusion, m6A RNA methylation regulators are closely correlated with CESC clinical characteristics and the selected six m6A RNA methylation regulators may be useful for CESC patients personalized treatment.

Cervical carcinoma (CC) has been associated with high morbidity, poor prognosis, and high intratumor heterogeneity. Necroptosis is the significant cellular signal pathway in tumors which may overcome tumor cells’ apoptosis resistance. To investigate the relationship between CC and necroptosis, we established a prognostic model based on necroptosis-related genes for predicting the overall survival (OS) of CC patients. The gene expression data and clinical information of cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) patients were obtained from The Cancer Genome Atlas (TCGA). We identified 43 differentially expressed necroptosis-related genes (NRGs) in CESC by examining differential gene expression between CESC tumors and normal tissues, and 159 NRGs from the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Gene ontology (GO) and KEGG enrichment analysis illustrated that the genes identified were mainly related to cell necrosis, extrinsic apoptosis, Influenza A, I − kappaB kinase/NF − kappaB, NOD − like receptor, and other signaling pathways. Subsequently, least absolute shrinkage and selection operator (LASSO) regression and univariate and multivariate Cox regression analyses were used to screen for NRGs that were correlated with patient prognosis. A prognostic signature that includes CAMK2A, CYBB, IL1A, IL1B, SLC25A5, and TICAM2 was established. Based on the prognostic model, patients were stratified into either the high-risk or low-risk subgroups with distinct survival. Receiver operating characteristic (ROC) curve analysis was used to identify the predictive accuracy of the model. In relation to different clinical variables, stratification analyses were performed to demonstrate the associations between the expression levels of the six identified NRGs and the clinical variables in CESC. Immunohistochemical (IHC) validation experiments explored abnormal expressions of these six NRGs in CESC. We also explored the relationship between risk score of this necroptosis signature and expression levels of some driver genes in TCGA CESC database and Gene Expression Omnibus (GEO) datasets. Significant relationships between the six prognostic NRGs and immune-cell infiltration, chemokines, tumor mutation burden (TMB), microsatellite instability (MSI), and immune checkpoints in CESC were discovered. In conclusion, we successfully constructed and validated a novel NRG signature for predicting the prognosis of CC patients and might also play a crucial role in the progression and immune microenvironment in CC.

Cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) tumorigenesis involves a combination of multiple genetic alteration processes. Constructing a survival-associated competing endogenous RNA (ceRNA) network and a multi-mRNA-based prognostic signature model can help us better understand the complexity and genetic characteristics of CESC. In this study, the RNA-seq data and clinical information of CESC patients were downloaded from The Cancer Genome Atlas. Differentially expressed mRNAs, lncRNAs and miRNAs were identified with the edgeR R package. A four-mRNA prognostic signature was developed by multivariate Cox regression analysis. Kaplan–Meier survival with the log-rank tests was performed to assess survival rates. The relationships between overall survival (OS) and clinical parameters were evaluated by Cox regression analysis. A survival-associated ceRNA network was constructed with the multiMiR package and miRcode database. Kyoto encyclopedia of genes and genomes (KEGG) analysis and gene ontology analyses were used to identify the functional role of the ceRNA network in the prognosis of CESC. A total of 298 differentially expressed mRNAs, 8 miRNAs, and 29 lncRNAs were significantly associated with the prognosis of CESC. A prognostic signature model based on 4 mRNAs (OPN3, DAAM2, HENMT1, and CAVIN3) was developed, and the prognostic ability of this signature was indicated by the AUC of 0.726. Patients in the high-risk group exhibited significantly worse OS. The KEGG pathways, TGF-β and Cell adhesion molecules, were significantly enriched. In this study, a CESC-associated ceRNA network was constructed, and a multi-mRNA-based prognostic model for CESC was developed based on the ceRNA network, providing a new perspective for cancer pathogenesis research.

Simple SummaryCervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) generally presents with HPV infection and is the second most common gynecological malignancy. However, the effect of immune infiltrate and immune microenvironment on the tumorigenesis and development of CESC remains unclear. In this study, we divided CESC cases into different immune subtypes and performed a differential gene expression analysis. The CESC cases (n = 303) were divided into five subtypes (C1–C5) based on their expression profiles. Subtype C4 demonstrated a downregulation of the immune profile, lower tumor immune/stroma scores, and worse prognosis, while subtype C1 showed the opposite characteristics. In addition, GSEA screened out some key genes associated with HPV infection pathways, among which high FOXO3 and low IGF-1 protein expression were closely correlated with decreased clinical prognosis. Our results may provide guidance for developing potential immunotherapeutic targets and biomarkers for CESC.Mounting evidence has highlighted the immune environment as a critical feature in the development of cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC). However, the relationship between the clinical characteristics of the immune environment and CESC remain unclear. Therefore, the aim of this study was to further characterize the relationship between the tumor and immune microenvironment and the clinical features of CESC using a variety of bioinformatic methods. Expression profiles (303 CESCs and three control samples) and relevant clinical data were obtained from The Cancer Genome Atlas. We divided CESC cases into different subtypes and performed a differential gene expression analysis. In addition, gene ontology (GO) and gene set enrichment analysis (GSEA) were performed to identify potential molecular mechanisms. Furthermore, data from 115 CESC patients from East Hospital were used to help identify the relationship between the protein expressions of key genes and disease-free survival using tissue microarray technology. Cases of CESC (n = 303) were divided into five subtypes (C1–C5) based on their expression profiles. A total of 69 cross-validated differentially expressed immune-related genes were identified. Subtype C4 demonstrated a downregulation of the immune profile, lower tumor immune/stroma scores, and worse prognosis. In contrast, the C1 subtype showed an upregulation of the immune profile, higher tumor immune/stroma scores, and better prognosis. A GO analysis suggested that changes in CESC were primarily enriched nuclear division, chromatin binding, and condensed chromosomes. In addition, GSEA demonstrated that cellular senescence, the p53 signaling pathway, and viral carcinogenesis are critical features of CESC. Moreover, high FOXO3 and low IGF-1 protein expression were closely correlated with decreased clinical prognosis. In summary, our findings provide novel insight into the relationship between the immune microenvironment and CESC. As such, our results may provide guidance for developing potential immunotherapeutic targets and biomarkers for CESC.

Mixed pedigree kinase 4 (MLK4) is a member of the serine/threonine kinases mixed pedigree kinase (MLKs) family. Few reports on immune-related targets in Cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), and the role of MLK4 in cervical cancer remains to be studied. The expression of MLK4 in CESC was analyzed by TCGA database containing 306 CESC tissues and 3 peritumoral tissue samples, and the effect of MLK4 on immune invasion was evaluated using the Deseq2 package(Benjamini-Hochberg corrected p-value < 0.05 and log2 fold change ≥|2|). Tissue microarray was used to verify the expression of MLK4 in CESC patients, and it was found that MLK4 was significantly overexpressed in CESC, and significantly correlated with WHO grade. Multiple analysis algorithms revealed that the high expression of MLK4 was negatively correlated with immune cell infiltration in CESC. Analysis showed that MLK4 expression was negatively correlated with the infiltration of various immune cells including CD8+T cells, and MLK4 mRNA expression was positively correlated with immune checkpoints PD-L1,CTLA4, LAG3, and negatively correlated with immune promotion genes CD86 and CD80. Furthermore, vitro assays were performed to investigate the biological characteristics of MLK4 in C33A cells. The EDU and transwell assays demonstrated that the decrease in MLK4 expression in C33A cells resulted in a decrease in cell proliferation and invasion. The silencing of MLK4 resulted in a significant increase in the expression of inflammatory cytokines IL-1β(p<0.05), TNF-α(p<0.01), and IL-6 (p<0.05). The results of cell assays indicate that knocking down MLK4 would inhibit the expression of established biochemical markers CEA, AFP and HCG. Hence, it is plausible that MLK4 could potentially exert a significant influence on the development and progression of Cervical cancer.

BackgroundCervical cancer is the fourth most common cancer in women. N6-dimethyladenosine (m6A) mRNA methylation is closely associated with cervical cancer.MethodsUsing TCGA database, we studied the expression and mutation of m6A-related genes in cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) and obtained genetic characteristics based on an m6A risk model and prognostic value of m6A. We studied the effects of the m6A risk score on immune features and genomic changes of patients with CESC, evaluated the sensitivity of patients with CESC to different small-molecule drugs based on the m6A risk score, and established a clinical prediction model.ResultsTen m6A-related genes were differentially expressed between CESC and normal tissues. High-risk patients had a low overall survival (OS) and significantly low immune scores but showed no significantly altered stromal scores. The tumor mutation burden (TMB) and tumor neoantigen levels significantly differed between the high- and low-risk groups. In the high-risk group, copy number variation (CNV) changes mainly led to gene amplification, while in the low-risk group, CNV changes primarily manifested as gene copy number deletions. ZC3H13 expression was low in CESC tissues. ZC3H13 knockdown promoted CESC cell proliferation, migration, and invasion, reducing the RNA methylation levels. Rapamycin suppressed the CESC cell proliferation, migration, and invasion abilities, increasing the m6A levels.Conclusionm6A mRNA methylation is closely related to the occurrence, development, immune invasion, drug sensitivity, and prognosis of cervical cancer. The prognostic m6A feature model of m6A signature genes can accurately predict the OS of patients with CESC. Drugs targeting factors regulating m6A mRNA methylation might offer a good prospect for treating cervical cancer.

The histone lysine methyltransferase SET (Suppressor of variegation, Enhancer of Zeste, Trithorax) and MYND (Myeloid-Nervy-DEAF1) domain-containing protein (SMYD2) plays a role in the tumorigenesis of cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC). However, the prognostic significance of SMYD2 in CESC and the link between SMYD2 and tumor-infiltrating immune cells are unknown. The prognostic value of SMYD2 in CESC was obtained from The Cancer Genome Atlas (TCGA). SMYD2 mRNA and protein were both highly expressed in CESC compared with normal tissues. The high expression of SMYD2 was associated with advanced tumor status and poor prognosis in CESC patients. SMYD2 was an independent prognostic factor for overall survival. In vitro experiments with knockdown of SMYD2 suppressed CESC cell migration and invasion. The online tumor immune estimation resource (TIMER) and Kaplan-Meier analysis results revealed that the infiltration of CD4+ T and CD8+ T cells was related to poor prognosis. In TIMER-based multivariate Cox regression analysis, CD8+ T cells and SMYD2 were demonstrated as independent prognostic factors of CESC. In conclusion, our data suggest that high SMYD2 expression is a predictor of poor prognosis in CESC patients; SMYD2 could serve as a prognostic biomarker and molecular therapeutic target for CESC.

Background: Nucleolar and spindle-associated protein 1 (NUSAP1) was previously reported to be associated with poor prognosis in multiple cancers. In the present study, we comprehensively investigated the clinicopathological features and potential prognostic value of NUSAP1 in cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC).Methods: The expression profiles of the genes were extracted from Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC), Cancer Cell Line Encyclopedia (CCLE), Gene Expression Profiling Interactive Analysis (GEPIA), and The Human Protein Atlas databases. The association between clinicopathological characteristics and NUSAP1 was analyzed using logistic regression in TCGA patients and receiver operating characteristic (ROC) curve analysis for GSE7803, GSE9750, and GSE63514 datasets. The prognostic value of NUSAP1 in TCGA patients was evaluated using the Kaplan-Meier method and Cox regression. Gene set enrichment analysis (GSEA) was conducted using TCGA dataset.Results: A total of 68 differentially expressed genes (DEGs) were identified in CESC. ROC analysis of NUSAP1 suggested that the area under the ROC curve was 0.968. Kaplan-Meier survival analysis indicated that CESC with low expression of NUSAP1 has a worse prognosis than CESC with high NUSAP1 expression (P = 0.005). The logistic regression revealed that low NUSAP1 expression in CESC was related to advanced tumor stage in TCGA database. Moreover, Cox regression analysis showed that NUSAP1 expression correlated significantly with prognosis in the case of patients in TCGA database. GSEA demonstrated that CESC patients with high expression of NUSAP1 were enriched in the G2M checkpoint, MYC targets, and breast cancer ZNF217.Conclusion: The results suggest that identification of DEGs might enhance our understanding of the causes and molecular mechanisms underlying the development of CESC. Moreover, NUSAP1 may play an important role in CESC progression and prognosis and may serve as a valuable indicator of poor survival in CESC.

Cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) are among the most prevalent gynecologic malignancies globally. The prognosis is abysmal once cervical cancer progresses to lymphatic metastasis. Anoikis, a specialized form of apoptosis induced by loss of cell adhesion to the extracellular matrix, plays a critical role. The prediction model based on anoikis-related genes (ARGs) expression and clinical data could greatly aid clinical decision-making. However, the relationship between ARGs and CESC remains unclear. ARGs curated from the GeneCards and Harmonizome portals were instrumental in delineating CESC subtypes and in developing a prognostic framework for patients afflicted with this condition. We further delved into the intricacies of the immune microenvironment and pathway enrichment across the identified subtypes. Finally, our efforts culminated in the creation of an innovative nomogram that integrates ARGs. The utility of this prognostic tool was underscored by Decision Curve Analysis (DCA), which illuminate its prospective benefits in guiding clinical interventions. In our study, We discerned a set of 17 survival-pertinent, anoikis-related differentially expressed genes (DEGs) in CESC, from which nine were meticulously selected for the construction of prognostic models. The derived prognostic risk score was subsequently validated as an autonomous prognostic determinant. Through comprehensive functional analyses, we observed distinctimmune profiles and drug response patterns among divergent prognosticstratifications. Further, we integrated the risk scores with the clinicopathological characteristics of CESC to develop a robust nomogram. DCA corroborated the utility of our model, demonstrating its potential to enhance patient outcomes through tailored clinical treatment strategies. The predictive signature, encompassing nine pivotal genes, alongside the meticulously constructed nomogram developed in this research, furnishes clinicians with a sophisticated tool for tailoring treatment strategies to individual patients diagnosed with CESC.

Cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) are major gynecological malignancies, causing significant cancer-related deaths in women. Current treatments yield poor outcomes, with a 5-year survival rate of only 17%. Identifying new biomarkers and therapeutic targets is crucial for improving prognosis and guiding personalized treatments. We analyzed TCEAL2 expression using data from The Cancer Genome Atlas (TCGA) across various cancers, including CESC. We explored its correlation with clinical features, prognosis, immune infiltration, MSI, mRNAsi, and drug sensitivity. TCEAL2 expression was validated in GSE9750 datasets and CESC cell lines using qRT-PCR. TCEAL2 expression was significantly dysregulated in CESC. Elevated TCEAL2 levels correlated with poor clinical outcomes, including advanced pathological M stage (p = 0.009), initial treatment failure (p = 0.0098), and reduced overall survival (OS) (p = 0.013). TCEAL2 was an independent predictor of unfavorable OS (p = 0.032). It was associated with key pathways such as calcium signaling, oxidative phosphorylation, and Wnt signaling. TCEAL2 also correlated with immune cell infiltration, MSI, and mRNAsi. Notably, TCEAL2 levels inversely correlated with sensitivity to several drugs, including CAY10603 and SB-223133. The results suggest that TCEAL2 plays a significant role in CESC progression and its tumor microenvironment. Its correlation with immune infiltration and drug sensitivity highlights its potential as a prognostic biomarker and therapeutic target. Future studies should focus on elucidating the molecular mechanisms and validating their clinical utility. TCEAL2 is a potential prognostic biomarker and therapeutic target in CESC. Further research is needed to explore its role and clinical applications.

BackgroundThe purpose of this study was to investigate the prognostic signature of necroptosis-related lncRNAs (NRLs) and explore their association with immune-related functions and sensitivity of the therapeutic drug in cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC).MethodsUCSC Xena provided lncRNA sequencing and clinical data about CESC, and a necroptosis gene list was obtained from the KEGG database. NRLs were selected by structuring a co-expression network of lncRNAs and necroptosis-related genes. To further screen lncRNAs, we used the univariate Cox regression method, Lasso regression, and multivariate Cox regression. Afterward, an NRL signature was established. We used the xCell algorithm and single-sample gene set enrichment analysis (ssGSEA) to clarify the pertinence between immune infiltration and NRL expressions in CESC patients and explored the relationship between the target lncRNAs and immune-related genes. By leveraging the GDSC database, the therapy-sensitive response of the prognostic signature was forecasted and an experimental validation was performed. We performed GSEA with the aim of recognizing the potential pathway related to the individual prognostic signature.ResultsThe two prognostic NRLs (AC009095.1 and AC005332.4) showed significant diversity and constituted the NRL signature. On the grounds of our signature, risk score was an independent element which was bound up with patient outcome (HR = 4.97 CI: 1.87–13.2, P = 0.001). The CESC patients were classified by the median risk score. Immune infiltration analysis revealed significant increases in CD4 + Tcm, eosinophils, epithelial cells, fibroblasts, NKT, plasma cells, platelets, and smooth muscle in the high-risk group (P< 0.05). Target lncRNAs also showed some correlation with NRGs. The estimated IC50 values of bicalutamide, CHIR.99021, and imatinib were lower in the high-risk group. Through the subsequent experimental validation, both AC009095.1 and AC005332.4 were significantly more highly expressed in SiHa than in Hela. AC009095.1 was expressed more highly in SiHa than in HUCEC, but the expression of AC005332.4 was reversed.ConclusionsThis study elucidated that NRLs, as a novel signature, were indispensable factors which can significantly influence the prognosis of patients with CESC and could provide novel clinical evidence to serve as a potential molecular biomarker for future therapeutic targets.

Cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) are among the most common malignancies of the female genital tract. Ferroptosis and immunity regulate each other and play important roles in the progression of CESC. The present study aimed to screen ferroptosis- and immune-related differentially expressed genes (FI-DEGs) to identify suitable prognostic signatures for patients with CESC. We downloaded the RNAseq count data and corresponding clinical information of CESC patients from The Cancer Genome Atlas database; obtained recognized ferroptosis- and immune-related genes from the FerrDb and ImmPort databases, respectively; and screened for suitable prognostic signatures using a series of bioinformatics analyses. We identified eight FI-DEGs (CALCRL, CHIT1, DES, DUOX1, FLT1, HELLS, SCD, and SDC1) that were independently correlated with the overall survival of patients with CESC. The prediction model constructed using these eight FI-DEGs was also independently correlated with overall survival. Both the sensitivity and specificity of the prediction model constructed using these eight signatures were over 60%. The comprehensive index of ferroptosis and immune status was significantly correlated with the immunity of patients with CESC. In conclusion, the risk assessment model constructed with these eight FI-DEGs predicted the CESC outcomes. Therefore, these eight FI-DEGs could serve as prognostic signatures for CESC.

Cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) is the most common malignancy of the female genital tract. MiR-1299 serves as a tumor suppressor, while KCNQ1OT1 acts as an oncogene in multiple malignancies. This research was designed to investigate the impacts of miR-1299 and KCNQ1OT1 on CESC progression. The downstream target of miR-1299 and the underlying regulatory mechanism of KCNQ1OT1 action on miR-1299 were explored. RT-qPCR was applied for RNA expression detection in CESC tissues and cells. RNA immunoprecipitation, RNA pulldown and luciferase reporter assays were applied to evaluate the binding between molecules in CESC cells. Cell Counting Kit-8 and colony formation assays were used for the measurement of CESC cell viability and proliferation. Western blotting was utilized to measure levels of apoptosis-related in CESC cells. MiR-1299 was downregulated in CESC tissues and presented a negative correlation with KCNQ1OT1 expression. KCNQ1OT1 was directly bound to miR-1299 to negatively modulate miR-1299 expression in CESC cells. The proliferative ability of CESC cells was suppressed by miR-1299 overexpression and was facilitated by KCNQ1OT1 overexpression. CESC cells apoptosis was promoted by miR-1299 mimics and inhibited by KCNQ1OT1 overexpression. In addition, in in vivo studies, miR-1299 overexpression rescued the effects of KCNQ1OT1 overexpression on CESC xenograft tumor growth. Finally, KCNQ1OT1 was bound to miR-1299 to upregulate PDPK1 expression in CESC cells. Collectively, miR-1299 was regulated by KCNQ1OT1 and inhibited CESC progression in vivo and in vitro, suggesting the tumor-suppressor role of miR-1299 for CESC.