Background The study purpose was to make investigation into the influence of XIST on cervical cancer progression and what’s more its potential mechanism. Methods The cervical cancer data sets (lncRNA, miRNA, and mRNA) obtained from TCGA were analyzed with the “mixOmics” R package. Then, the expression of XIST, miR-140-5p, and ORC1 were detected using qRT-PCR and western blot in both tissues and cervical cancer cell lines (Hela and C33A) to verify the bioinformatics analyses results. CCK-8 assay, 5-ethynyl-2′-deoxyuridine (EdU) assays, cell cycle assay and cell apoptosis assay were practiced. Besides, immunohistochemistry staining was operated for the detection of the Ki-67, E-cadherin and vimentin expression in cervical cancer tissues and the apoptosis-related proteins expression (c-caspase3, Bcl-2, total PARP and cleaved PARP) was verified through western blot. And in vivo experiments were implemented. Results MiR-140-5p was down-regulated but XIST and ORC1 were up-regulated in cervical cancer tissues and cell lines. Knocking down of the XIST or ORC1 memorably suppressed cell proliferation, blocked cell cycle, decreased the expression of Bcl-2 while increased the apoptosis rate and the expression of c-caspase3 and cleaved PARP in HeLa and C33A cells. Besides, the results of immunohistochemistry staining showed knocking down the expression of XIST improved the expression levels of E-cadherin and decreased Ki-67 and vimentin expression. And overexpression of miR-140-5p also could inhibit the progression and reverse the influence of XIST and ORC1 in HeLa and C33A cells. Conclusion Our study indicated the effects of XIST/miR-140-5p/ ORC1 axis on the progression of cervical cancer which will shed new light on epigenetic diagnostics and therapeutics in cervical cancer.

No abstract

High-risk HPV (hrHPV) is related to cervical carcinogenesis, although clinical data comparing the natural history and carcinogenic potential of type-specific HPV remain limited. Furthermore, the nationwide prevalence rates of overall and type-specific HPV among women with cervical precancerous lesions and cancer have not been reported. Here, a meta-analysis was performed for type-specific HPV distribution among 30,165 HPV-positive women, including 12,094 invasive cervical cancers (ICCs), 10,026 cervical intraepithelial neoplasia grade 2/3 (CIN2/3), 3246 CIN1, and 4799 normal cervices from 45 PCR-based studies. We found that HPV16 was the most common hrHPV type involved in cervical disease. The HPV16 positivity rate varied little across normal (22.7%) and CIN1 individuals (23.6%) but increased through the CIN2 (37.6%) and CIN3 patients (51.9%) to 65.6% in ICC cases. HPV16, 18, 35, 39, 45, and 59 were more frequent in ICC than CIN3, with ICC:CIN3 ratios ranging from 2.3 for HPV18 to 1.1 for HPV35/45. HPV31, 33, 52, and 58 were more frequent in CIN3 compared with normal cervices but less common in ICC compared with CIN3 (ICC:CIN3 ratios ranging from 0.6 for HPV58 and 0.4 for HPV52). The ICC:normal ratios were particularly high for HPV18, 52 and 58 in West China (4.1, 3.9 and 2.9, respectively) and for HPV45 and 59 in North China (1.6 and 1.1, respectively). In summary, this study is the most comprehensive analysis of type-specific HPV distribution in cervical carcinogenesis and could be valuable for HPV-based cervical cancer screening strategies and vaccination policies in China.

Abstract. Forkhead box (FOX) A1 is a member of the FOX family of transcription factors, which serve a function in numerous types of tumor. The present study assessed the potential role of FOXA1 in human epithelial ovarian carcinoma (EOC). Total RNA was isolated from 16 fresh-frozen EOC tumors with paired corresponding non-malignant ovarian epithelium tissues, and FOXA1 expression was analyzed using reverse transcription-quantitative polymerase chain reaction. Immunohistochemical analysis was performed to evaluate FOXA1 expression in 110 epithelial ovarian carcinoma tissue specimens (including 80 serous papillary adenocarcinoma, 9 clear cell carcinoma, 12 endometrioid adenocarcinoma, 5 mucinous carcinoma and 4 transitional cell carcinoma specimens), 24 benign ovarian tumor surface epithelium tissues and 10 normal ovarian tissue samples. The present study analyzed the association between FOXA1 expression and clinical characteristics in patients with EOC. The Kaplan-Meier method was used for survival analysis. The results of the present study revealed that FOXA1 mRNA expression was significantly increased in EOC tissues compared with paired normal ovarian samples (P=0.014). The immunohistochemical expression of FOXA1 in EOC tissues was associated with the FIGO grade, differentiation status and overall survival time (all P<0.05). Finally, the significance of FOXA1 expression in the prognosis of the patients was evaluated. The results of Kaplan-Meier survival curve revealed that high FOXA1 expression was associated with decreased overall survival time in the patients, relative to low FOXA1 expression (P=0.0132). In conclusion, FOXA1 is overexpressed in EOC and associated with clinicopathological features, including overall survival time. FOXA1 potentially represents a novel biomarker and therapeutic target for EOC.