Long non-coding RNA XIST regulates ovarian cancer progression via modulating miR-335/BCL2L2 axis

Abstract

Background X inactivation-specific transcript (XIST) is the long non-coding RNA (lncRNA) related to cancer, which is involved in the development and progression of various types of tumor. However, up to now, the exact role and molecular mechanism of XIST in the progression of ovarian cancer are not clear. We studied the function of XIST in ovarian cancer cells and clinical tumor specimens. Methods RT-qPCR was performed to detect the expression levels of miR-335 and BCL2L2 in ovarian cancer cells and tissues. MTT and transwell assays were carried out to detect cell proliferation, migration, and invasion abilities. Western blot was performed to analyze the expression level of BCL2L2. The interaction between miR-335 and XIST/BCL2L2 was confirmed using a luciferase reporter assay. Results The inhibition of XIST can inhibit the proliferation invasion and migration of human ovarian cancer cells. In addition, the miR-335/BCL2L2 axis was involved in the functions of XIST in ovarian cancer cells. These results suggested that XIST could regulate tumor proliferation and invasion and migration via modulating miR-335/BCL2L2. Conclusion XIST might be a carcinogenic lncRNA in ovarian cancer by regulating miR-335, and it can serve as a therapeutic target in human ovarian cancer.

The lncRNAs at X Chromosome Inactivation Center: Not Just a Matter of Sex Dosage Compensation

“…In fact, growing evidence linking pathological conditions to lncRNAs and their regulatory network is emerging, especially in cancer development and progression, with important implications in diagnostics and therapeutics. Specifically, different studies report the correlation of XIST expression with prognosis such as in the case of colon and gastric cancer, glioma and cervical and ovarian cancer [ 65 , 66 , 67 , 68 , 69 , 76 , 77 , 78 , 79 , 83 , 84 , 85 , 86 ] or FTX expression and gastric cancer prognosis [ 179 ] or JPX expression and poor survival of lung cancer patients [ 188 , 189 ]; probably, combination of the expression values of more than one RNA molecule involved in the same regulatory axis could enhance the diagnostic power, e.g., making it possible to stratify the patients according tumor stage, favorable/unfavorable outcome and even therapy effectiveness. Finally, understanding the versatility of RNA biology has become a stepping stone for RNA therapeutics that has definitely demonstrated its power [ 13 ].…”

“…Finally, understanding the versatility of RNA biology has become a stepping stone for RNA therapeutics that has definitely demonstrated its power [ 13 ]. Various therapeutic strategies can be based on boosting the expression level of a “beneficial” miRNA or inhibiting a harmful one; of note, different studies demonstrated that knock-down of a lncRNA such as XIST [ 68 , 69 , 75 , 76 , 77 , 78 , 79 , 83 , 84 , 85 , 86 ], or FTX [ 176 ] and JPX [ 188 , 189 ], exerts tumor-suppressive functions in vitro and in vivo, validating new therapeutic targets. In the near future, some of the predicted RNA interactions among lncRNAs/miRNAs/mRNAs that have not been included here could be experimentally validated, especially by in vivo studies, allowing a comprehensive view and envisaging new therapeutic opportunities by manipulating the network.…”

“…In ovarian cancer, XIST, miR-140-5p and the transcriptional factor FOXP3 engage a ceRNET, driving ovarian cancer cell progression: XIST was found upregulated in cancer tissues and correlated to poor prognosis of patients; conversely, miR-149-3p was found downregulated with the consequent upregulation of its target, FOXP3; XIST knock-down elevated miR-149-3p to suppress migration and invasion of ovarian cancer cells, and restricted tumor growth in vivo [ 85 ]. A similar regulatory network has been identified, whereby XIST regulated proliferation, invasion and migration via the miR-335/BCL2L2 axis [ 86 ].…”

Decreased exosome-delivered miR-486-5p is responsible for the peritoneal metastasis of gastric cancer cells by promoting EMT progress

“…After washing with tris-buffered saline with 0.1% Tween® 20 detergent (TBST) buffer, the membrane was incubated with 5% bovine serum albumin (BSA) to remove the non-specific binding proteins, followed by being washed and incubated with primary antibodies against CD9 (1:1000, CST, Boston, USA), CD63 (1:1000, CST, Boston, USA), CD81 (1:1000, CST, Boston, USA), E-cadherin (1:1000, CST, Boston, USA), α -SMA (1:1000, CST, Boston, USA), Snail (1:1000, CST, Boston, USA), ACTR3 (1:1000, CST, Boston, USA), or GAPDH (1:1000, CST, Boston, USA) at 4 °C overnight. Subsequently, the membrane was washed and incubated with the secondary antibody (1:500, CST, Boston, USA) at room temperature for 1.5 h. Finally, the bands were exposed to Tanon 1600/1600R (Tanon, Shanghai, China) after adding the ECL solution and the images were quantified using the Image J software [ 24 ].…”

Long noncoding RNA XIST: Mechanisms for X chromosome inactivation, roles in sex-biased diseases, and therapeutic opportunities

“… 153 These findings indicate that XIST might not only be a biomarker for the diagnosis and prognosis of cancers, but also a potential therapeutic target for ovarian cancer. Notably, two recent studies have claimed that XIST promotes the proliferation, invasion, and migration of ovarian cancer cells by modulating the miR-335/BCL2L2 axis 157 and regulating miR-149-3p. 158 These findings require reconciliation with prior observations.…”