TRA2A Binds With LncRNA MALAT1 To Promote Esophageal Cancer Progression By Regulating EZH2/β-catenin Pathway

Xing Zhao; Qiuyang Chen; Yujie Cai; Danze Chen; Mingrong Bei; Hongyan Dong; Jianzhen Xu

doi:10.7150/jca.55661

TRA2A Binds With LncRNA MALAT1 To Promote Esophageal Cancer Progression By Regulating EZH2/β-catenin Pathway

J Cancer. 2021 Jun 11;12(16):4883-4890. doi: 10.7150/jca.55661. eCollection 2021.

Authors

Xing Zhao^{1

2}, Qiuyang Chen¹, Yujie Cai¹, Danze Chen¹, Mingrong Bei¹, Hongyan Dong³, Jianzhen Xu¹

Affiliations

¹ Computational Systems Biology Lab, Department of Bioinformatics, Shantou University Medical College (SUMC), No. 22, Xinling Road, Shantou, China.
² Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
³ Department of Pathology, Linyi People's Hospital, Linyi, China.

Abstract

The RNA binding protein TRA2A, a member of the transformer 2 homolog family, plays a crucial role in the alternative splicing of pre-mRNA. However, it remains unclear whether TRA2A is involved in non-coding RNA regulation and, if so, what are the functional consequences. By analyzing expression profiling data, we found that TRA2A is highly expressed in esophageal cancer and is associated with disease-free survival and overall survival time. Subsequent gain- and loss-of-function studies demonstrated that TRA2A promotes proliferation and migration of esophageal squamous cell carcinoma and adenocarcinoma cells. RNA immunoprecipitation and RNA pull-down assay indicated that TRA2A can directly bind specific sites on MALAT1 in cells. In addition, ectopic expression or depletion of TRA2A leads to MALAT expression changes accordingly, thus modulates EZH2/β-catenin pathway. Together, these findings elucidated that TRA2A triggers carcinogenesis via MALAT1 mediated EZH2/β-catenin axis in esophageal cancer cells.

Keywords: Esophageal cancer; MALAT1; TRA2A.