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

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.

MiR-18a increased the permeability of BTB via RUNX1 mediated down-regulation of ZO-1, occludin and claudin-5

“…MiR-18a has shown different expression levels in different tumors. Previous studies have reported that miR-18a was highly expressed and exerted an oncogenic role across a wide spectrum of human solid cancers [25][26][27]. However, miR-18a expression was not changed compared with that of control K562 cells for reasons yet to be clarified, despite other members of the miR-17-92 cluster being upregulated in lentivirally transduced K562 clones [28].…”

miR-18a counteracts AKT and ERK activation to inhibit the proliferation of pancreatic progenitor cells

“…AKT activity leads to the downsteam phosphorylation of mammalian targets of rapamycin (mTOR), further regulating cyclinD1 and c-myc expression40. miR-18a inhibits AKT phosphorylation, thus reducing the sensitivity of mTORC1, and its two substrates S6K1 and 4E-BPl3841, further repressing cell cycle progression by downregulating cyclinD gene expression and activating P21 and P27 (Fig. 2D).…”

miR-31 affects colorectal cancer cells by inhibiting autophagy in cancer-associated fibroblasts

“…Studies have also reported that miRNAs play regulatory roles in the autophagy of colon cancer cells. For example, Qased AB found that overexpression of miR-18a inhibited mTORC1 activity to prevent the occurrence of colon cancer in HCT116 cells through the induction of autophagy [21]. Therefore, miRNAs regulate all stages of tumor cell autophagy.…”