MicroRNA-18a upregulates autophagy and ataxia telangiectasia mutated gene expression in HCT116 colon cancer cells

Qased,Abu Baker; Yi,Heqing; Liang,Nan; Ma,Shumei; Qiao,Shixing; Liu,Xiaodong

doi:10.3892/mmr.2012.1214

MicroRNA-18a upregulates autophagy and ataxia telangiectasia mutated gene expression in HCT116 colon cancer cells

Authors:
- Abu Baker Qased
- Heqing Yi
- Nan Liang
- Shumei Ma
- Shixing Qiao
- Xiaodong Liu
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Affiliations: Department of Surgery, College of Medicine, University of Mosul, Mosul, Iraq, Key Laboratory of Radiobiology (Ministry of Health), School of Public Health, Jilin University, Changchun, Jilin, P.R. China, Department of Surgery, The Second Hospital of Jilin University, Changchun, Jilin, P.R. China
Published online on: December 3, 2012 https://doi.org/10.3892/mmr.2012.1214
Pages: 559-564

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Abstract

Autophagy is an evolutionarily conserved, multi-step lysosomal degradation process in which a cell degrades its own long-lived proteins and damaged organelles. Ataxia telangiectasia mutated (ATM) has recently been shown to upregulate the process of autophagy. Previous studies showed that certain microRNAs, including miR-18a, potentially regulate ATM in cancer cells. However, the mechanisms behind the modulation of ATM by miR-18a remain to be elucidated in colon cancer cells. In the present study, we explored the impact of miR-18a on the autophagy process and ATM expression in HCT116 colon cancer cells. To determine whether a preliminary link exists between autophagy and miR-18a, HCT116 cells were irradiated and quantitative (q) PCR was performed to measure miR-18a expression. HCT116 cells were transfected with an miR-18a mimic to study its impact on indicators of autophagy. Western blotting and luciferase assays were implemented to explore the impact of miR-18a on ATM gene expression in HCT116 cells. The results showed that miR-18a expression was strongly stimulated by radiation. Ectopic overexpression of miR-18a in HCT116 cell lines potently enhanced autophagy and ionizing radiation-induced autophagy. Moreover, miR-18a overexpression led to the upregulation of ATM expression and suppression of mTORC1 activity. Results of the present study pertaining to the role of miR-18a in regulating autophagy and ATM gene expression in colon cancer cells revealed a novel function for miR-18a in a critical cellular event and on a crucial gene with significant impacts in cancer development, progression, treatment and in other diseases.

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