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

Shao-Hua Zhuang, Chu-Chen Meng, Jin-Jin Fu, Jian Huang

The Kaohsiung journal of medical sciences 2022 Jul

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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. © 2022 The Authors. The Kaohsiung Journal of Medical Sciences published by John Wiley & Sons Australia, Ltd on behalf of Kaohsiung Medical University.

Citation

Shao-Hua Zhuang, Chu-Chen Meng, Jin-Jin Fu, Jian Huang. Long non-coding RNA ELFN1-AS1-mediated ZBTB16 inhibition augments the progression of gastric cancer by activating the PI3K/AKT axis. The Kaohsiung journal of medical sciences. 2022 Jul;38(7):621-632