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

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.

RETRACTED: Long Noncoding RNA FOXD2-AS1 Promotes the Malignancy of Cervical Cancer by Sponging MicroRNA-760 and Upregulating Hepatoma-Derived Growth Factor

“…They can function as molecular sponges, scaffolds, and guides for interactions with proteins, mRNAs, or microRNAs (miRNAs), thereby regulating the expression of target genes (Anastasiadou et al, 2018). Accumulated evidence indicates that many lncRNAs are aberrantly expressed in cervical cancer (Chen et al, 2019;Zhang X. et al, 2019). Alterations in the expression of lncRNAs are involved in cervical carcinogenesis and cancer progression by playing tumorsuppressive or oncogenic roles (Aalijahan and Ghorbian, 2019).…”

miR‐451a inhibits cancer growth, epithelial‐mesenchymal transition and induces apoptosis in papillary thyroid cancer by targeting PSMB8

“…miRNAs bind to the seed sequences of the 3’‐untranslated region of their target messenger RNAs (mRNAs) and mediate the degradation of corresponding mRNAs or inhibit their translation . Multiple studies have reported the correlation between aberrant expression of miRNAs and cancer progression . Furthermore, free miRNAs could be detected in human body fluids like serum.…”

“…8 Multiple studies have reported the correlation between aberrant expression of miRNAs and cancer progression. [9][10][11][12] Furthermore, free miRNAs could be detected in human body fluids like serum. The expression profile of cancer patients' serum miRNAs differs significantly from healthy people's expression profile.…”

<p>Long Non-Coding RNA TMPO-AS1 Promotes Cervical Cancer Cell Proliferation, Migration, and Invasion by Regulating miR-143-3p/ZEB1 Axis</p>

“…They also found that SOX21-AS1 promoted cervical cancer progression and could be used as a potential prognostic biomarker for patients with cervical cancer. Also, Chen et al 16 demonstrated that lncRNA X-inactive specific transcript (XIST) contributed to progression of cervical cancer by sponging miR-140-5p. Here, we detected lncRNA TMPO-AS1 expression in cervical cancer cells and found that TMPO-AS1 was highly expressed in cervical cancer cells.…”