BTEB2-Activated lncRNA TSPEAR-AS2 Drives GC Progression through Suppressing GJA1 Expression and Upregulating CLDN4 Expression

Long non-coding RNAs (lncRNAs) are characterized as key layers of the genome in various cancers. TSPEAR-AS2 was highlighted to be a candidate lncRNA potentially involved in gastric cancer (GC) progression. However, the clinical significance and mechanism of TSPEAR-AS2 in GC required clarification. T...

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Published in:Molecular therapy. Nucleic acids 2020-12, Vol.22, p.1129-1141
Main Authors: Ma, Zhong-Hua, Shuai, You, Gao, Xiang-Yu, Yan, Yan, Wang, Ke-Ming, Wen, Xian-Zi, Ji, Jia-Fu
Format: Article
Language:English
Subjects:
BTEB2
gastric cancer
long non-coding RNA
Original
TSPEAR-AS2
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Summary:Long non-coding RNAs (lncRNAs) are characterized as key layers of the genome in various cancers. TSPEAR-AS2 was highlighted to be a candidate lncRNA potentially involved in gastric cancer (GC) progression. However, the clinical significance and mechanism of TSPEAR-AS2 in GC required clarification. The clinical significance of TSPEAR-AS2 was elucidated through Kaplan-Meier Plotter. The mechanism of TSPEAR-AS2 in GC was clarified in vitro and in vivo using luciferase reporter, chromatin immunoprecipitation, RNA immunoprecipitation assays, and animal models. TSPEAR-AS2 elevation was closely correlated with overall survival of GC patients. A basic transcription element-binding protein 2 (BTEB2)-activated TSPEAR-AS2 model was first explored in this study. TSPEAR-AS2 silencing substantially reduced tumorigenic capacities of GC cells, while TSPEAR-AS2 elevation had the opposite effect. Mechanistically, TSPEAR-AS2 bound with both polycomb repressive complex 2 (PRC2) and argonaute 2 (Ago2). TSPEAR-AS2 knockdown significantly decreased H3K27me3 levels at promoter regions of gap junction protein alpha 1 (GJA1). Ago2 was recruited by TSPEAR-AS2, which was defined to sponge miR-1207-5p, contributing to the repression of claudin 4 (CLDN4) translation. The axis of EZH2/GJA1 and miR-1207-5p/CLDN4 mediated by BTEB2-activated-TSPEAR-AS2 plays an important role in GC progression, suggesting a new therapeutic direction in GC treatment. [Display omitted] Ma and colleagues elucidated the clinical significance and mechanism of lncRNA TSPEAR-AS2 in gastric cancer progression. The regulatory axis of EZH2/GJA1 and miR-1207-5p/CLDN4 mediated by BTEB2-activated-TSPEAR-AS2 suggested a new therapeutic direction for patients with gastric cancer.
ISSN:2162-2531
2162-2531
DOI:10.1016/j.omtn.2020.10.022