| Autor: |
Zhong-Hua Ma, You Shuai, Xiang-Yu Gao, Yan Yan, Ke-Ming Wang, Xian-Zi Wen, Jia-Fu Ji |
| Jazyk: |
angličtina |
| Rok vydání: |
2020 |
| Předmět: |
|
| Zdroj: |
Molecular Therapy: Nucleic Acids, Vol 22, Iss , Pp 1129-1141 (2020) |
| Druh dokumentu: |
article |
| ISSN: |
2162-2531 |
| DOI: |
10.1016/j.omtn.2020.10.022 |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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