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Cancer Lett. 2019 May 1;449:226-236. doi: 10.1016/j.canlet.2019.02.026. Epub 2019 Feb 16.

MIR-1265 regulates cellular proliferation and apoptosis by targeting calcium binding protein 39 in gastric cancer and, thereby, impairing oncogenic autophagy.

Author information

1
Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu province, China.
2
Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu province, China; Collaborative Innovation Center For Cancer Personalized Medicine, Nanjing Medical University, Nanjing, 210029, Jiangsu province, China. Electronic address: xuzekuan@njmu.edu.cn.

Abstract

Increasing evidence indicates that microRNAs (miRNAs) play an important role in various tumors by regulating downstream target genes and diverse signaling pathways. Herein, we confirmed miR-1265 expression in gastric cancer (GC) using the Cancer Genome Atlas (TCGA) database and assessed the level of miR-1265 expression in clinical specimens and cell lines. We found that miR-1265 expression was negatively correlated with tumor size. Further functional analysis revealed that miR-1265 suppresses cellular proliferation and autophagy while inducing apoptosis in GC cells. A luciferase reporter assay was used to identify an miR-1265 targeted gene, calcium binding protein 39 (CAB39), which is an essential upstream regulator in the AMPK-mTOR signaling pathway. Upregulation or downregulation of CAB39 expression reversed the effects of miR-1265 overexpression or inhibition, respectively. Notably, the knockdown of autophagy-related gene 12 (ATG12) impaired the effects of miR-1265 inhibition or CAB39 overexpression in GC. MiR-1265 also suppressed the growth of GC cells in vivo and that of human gastric organoids. Altogether, our results show that miR-1265 suppresses GC progression and oncogenic autophagy by reducing CAB39 expression and regulating the AMPK-mTOR signaling pathway. Therefore, miR-1265 may represent a potential therapeutic target for GC.

KEYWORDS:

AMPK; Gastric cancer; Organoid; miR-1265

PMID:
30779944
DOI:
10.1016/j.canlet.2019.02.026
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