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The Long Non-Coding RNA XIST Interacted with MiR-124 to Modulate Bladder Cancer Growth, Invasion and Migration by
Yaoyao Xiong1, Long Wang2, Yuan Li2
1Department of Cardiopulmonary Bypass, The Second Xiangya Hospital, Central South University, Changsha, China.
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.
Insights
Long non-coding RNA XIST promotes bladder cancer by regulating miR-124 and androgen receptor (AR). This oncogenic lncRNA drives tumor growth, invasion, and migration, highlighting potential therapeutic targets.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Long non-coding RNA XIST is implicated in various tumor progressions.
- Interactions between lncRNAs, microRNAs (miRNAs), and target genes are crucial in malignancy.
- Androgen receptor (AR) plays a role in bladder cancer progression.
Purpose of the Study:
- Investigate the role of XIST in human bladder cancer.
- Elucidate the interaction between XIST, miR-124, and AR in bladder cancer.
Main Methods:
- XIST and AR expression analysis in bladder tumor tissues and cell lines.
- Functional assays assessing XIST and AR effects on bladder cancer cell proliferation, invasion, and migration.
- Bioinformatic analysis, luciferase assays, and correlation studies to determine molecular interactions and clinical relevance.
Main Results:
- XIST and AR were upregulated and positively correlated in bladder cancer tissues, associated with advanced TNM stage.
- XIST knockdown inhibited bladder cancer cell growth and metastasis, effects partially reversed by AR overexpression.
- XIST directly targeted and inhibited miR-124, which in turn regulated AR expression. MiR-124 levels were inversely correlated with XIST and AR expression in tumor tissues.
Conclusions:
- XIST acts as an oncogenic lncRNA in bladder cancer.
- XIST promotes tumor growth, invasion, and migration through a mechanism involving miR-124-dependent regulation of AR.
- Findings suggest XIST as a potential therapeutic target for bladder cancer.
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