The Long Non-Coding RNA XIST Interacted with MiR-124 to Modulate Bladder Cancer Growth, Invasion and Migration by Targeting Androgen Receptor (AR)

Abstract

Backgrounds/Aims: Long non-coding RNA (lncRNA) X-inactive specific transcript (XIST) is involved in the progression of several tumors. The interaction between lncRNA and miRNA or miRNA’s target genes is reported to play crucial roles in malignancy. In addition, Androgen receptor (AR) is considered to be involved in bladder cancer progression. In this study, we investigated the role of XIST in human bladder cancer and its interaction with miR-124 and AR. Methods: XIST and AR expression was detected in bladder tumor samples and cell lines. Effects of XIST and AR on bladder cancer cells growth, invasion and migration were analyzed. Bioinformatic analysis and luciferase assays were used to identify the interaction among XIST, AR and miR-124. The correlations of miR-124 with XIST and AR in bladder cancer samples were statistically analyzed. Results: XIST and AR were upregulated in bladder cancer tissues and positively correlated. Higher XIST and AR expression were related to poorer TNM stage of bladder cancer. XIST knockdown reduced bladder cancer cells’ proliferation, invasion and migration. While this inhibitory effect could be partially restored by AR overexpression. XIST inhibited miR-124 expression by directly targeting. Moreover, miR-124 could bind to the 3’UTR of AR to regulate its expression. MiR-124 inhibition partially restored the XIST knockdown-induced reduction of AR, c-myc, p27, MMP13 and MMP9 expression. In bladder cancer tissues, miR-124 level was inversely correlated with the expression of XIST and AR, respectively. Conclusion: These findings indicated that XIST might be an oncogenic lncRNA that promoted the bladder cancer growth, invasion and migration via miR-124 dependent AR regulation.

Knockdown of Long Non-Coding RNA XIST Inhibited Doxorubicin Resistance in Colorectal Cancer by Upregulation of miR-124 and Downregulation of SGK1

“…Recent studies suggest that lncRNAs can suppress the expressions and biological functions of miRNAs by functioning as a molecular sponge or a competing endogenous RNA (ceRNA), hence leading to derepression of its target mRNA [17]. Interestingly, XIST was reported to directly interact with miR-124 to modulate bladder cancer progression [18]. Therefore, this study was designed to investigate whether XIST could interact with miR-124 to participate in the regulation of DOX resistance in CRC.…”

Immune Checkpoint Human Endogenous Retrovirus-H Long Terminal Repeat-Associating Protein 2 is Upregulated and Independently Predicts Unfavorable Prognosis in Bladder Urothelial Carcinoma

“…Consistently, in this study, we found that HHLA2 is upregulated in BUC tissues compared with normal tissues, and high HHLA2 expression predicts poor survival in BUC patients. BCa is manifested with highly recurrent multiple tumors [22,23]. Clinical tumor staging, pathological grade, and lymph node metastasis have been proven to be vital predictors of clinical prognosis [24].…”

CircRNA-Cdr1as Exerts Anti-Oncogenic Functions in Bladder Cancer by Sponging MicroRNA-135a

“…For example, microRNAs may regulate the proliferation, migration, invasion [4, 5] and the chemo-sensitivity [6] of bladder cancer. Long Non-coding RNAs also showed huge functions in bladder cancer，including tumorigenesis, growth [7], apoptosis [8], metastasis [9] and so on. Recently, circRNAs have been found own great influence in cancer.…”