Long non-coding RNA XIST promotes cell growth and metastasis through regulating miR-139-5p mediated Wnt/β-catenin signaling pathway in bladder cancer.

Yangyang Hu,Chao Deng,Jing Zhang,Bo Peng,He Zhang,Chuanyi Hu

doi:10.18632/oncotarget.21791

Yangyang Hu, Chao Deng + Show 4 more

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https://doi.org/10.18632/oncotarget.21791

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Abstract

Bladder cancer is one of the most common urological malignancy all over the world. Recently, long non-coding RNA (lncRNA) XIST has been identified as an oncogenic gene in several type of cancers. However, the expression level and functional role of XIST in bladder cancer remain largely unknown. In the present study, we found that XIST was significantly up-regulated in bladder cancer tissues and cell lines, and was correlated with poor prognosis of bladder cancer patients. Furthermore, XIST knockdown significantly inhibited bladder cancer cell growth and metastasis in vitro and tumor growth in vivo. We also demonstrated that XIST acted as a competing endogenous RNA for miR-139-5p and repression of miR-139-5p could restore the inhibitory effects on bladder cancer cells induced by XIST shRNA. In addition, we identified that Wnt1 was a direct target of miR-139-5p, and XIST played the oncogenic role in bladder cancer by activating the Wnt/β-catenin signaling pathway. Taken together, our study suggested that lncRNA XIST may serve as a prognostic biomarker and a potential therapeutic target for bladder cancer.

Highlights

Bladder cancer is one of the most common urological malignancy all over the world [1]
These results provide the evidence that the regulatory mechanism of newly identified long non-coding RNA (lncRNA) X-inactive specific transcript (XIST)/miR-139-5p/Wnt1 axis in carcinogenesis and metastasis of bladder cancer, which may shed new light on lncRNA-directed applications in cancer diagnosis and therapy
Yao et al indicated that XIST expression was up-regulated in glioma tissues and human glioblastoma stem cells, knockdown of XIST exerted tumor-suppressive functions by inhibiting cell proliferation, migration and invasion as well as promoting apoptosis [26]

Summary

Introduction

Bladder cancer is one of the most common urological malignancy all over the world [1]. Surgical resection and chemotherapy remain the curative strategies for bladder cancer treatment [2]. Despite there have been great improvements in current clinical treatment for bladder cancer such as adjuvant chemo-radiotherapies and immunological therapy, the five-year overall survival rate is far from satisfactory [3,4,5]. It is urgent need to explore the molecular mechanisms underlying bladder cancer tumorigenesis and progression to discover novel molecular biomarkers and therapeutic strategies for bladder cancer. Recent emerging evidences have shown that lncRNAs play important roles in the development of human diseases, especially in cancers [9, 10]

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