Up-regulated lncRNA XIST contributes to progression of cervical cancer via regulating miR-140-5p and ORC1

• Main Authors: Xing Chen, Dongsheng Xiong, Liya Ye, Kai Wang, Lingfei Huang, Shuangshuang Mei, Jinhong Wu, Shanshan Chen, Xiaoli Lai, Lingzhi Zheng, Meifen Wang
• Format: Article
• Language: English
• Published: BMC 2019-02-01
• Series: Cancer Cell International
• Subjects: XIST; miR-140-5p; ORC1; Cervical cancer cells
• Online Access: http://link.springer.com/article/10.1186/s12935-019-0744-y

Abstract 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.