Long non‐coding RNA ELFN1‐AS1‐mediated ZBTB16 inhibition augments the progression of gastric cancer by activating the PI3K/AKT axis

Autor: Shao‐Hua Zhuang, Chu‐Chen Meng, Jin‐Jin Fu, Jian Huang
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Kaohsiung Journal of Medical Sciences, Vol 38, Iss 7, Pp 621-632 (2022)
Druh dokumentu: article
ISSN: 2410-8650
1607-551X
DOI: 10.1002/kjm2.12548
Popis: Abstract Long non‐coding RNA ELFN1 antisense RNA 1 (ELFN1‐AS1) has been reported as a cancer driver in many human malignancies. This study was conducted to investigate the function of ELFN1‐AS1 in gastric cancer (GC) and its mechanism of action. Bioinformatics analysis revealed increased expression of ELFN1‐AS1 in GC, and abundant expression of ELFN1‐AS1 was observed in the acquired GC cell lines. Knockdown of ELFN1‐AS1 in GC cells weakened cell proliferation, invasion, migration, and resistance to apoptosis. ELFN1‐AS1 was mainly localized in the nuclei of GC cells. ELFN1‐AS1 recruited DNA methyltransferases to the promoter region of ZBTB16 and induced transcriptional repression of ZBTB16 through methylation modification. Furthermore, downregulation of ZBTB16 activated the phosphatidylinositol 3‐kinase/protein kinase B (PI3K/AKT) signaling pathway and restored the proliferation and invasiveness of GC cells. In vivo, downregulation of ELFN1‐AS1 reduced the growth rate of xenograft tumors in mice. In summary, this study demonstrates that ELFN1‐AS1 recruits DNA methyltransferases to the promoter region of ZBTB16 to induce its transcriptional repression, which further augments the development of GC by activating the PI3K/AKT signaling pathway.
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