TY - JOUR AB - Colorectal cancer (CRC) is a leading cause of cancer-related death worldwide. Deregulation of microRNAs (miRNAs) has been reported to participate in CRC progression. In the present study, we observed downregulation of miR-218 and upregulation of YEATS domain containing 4 (YEATS4) in CRC tissues and in multidrug-resistant HCT-116/L-OHP cells compared with these levels in normal tissues and parental HCT-116 cells, respectively. The results indicated that miR-218 overexpression significantly decreased the IC50 value of oxaliplatin (L-OHP) in the HCT-116/L-OHP cells, and suppression of miR-218 significantly enhanced the IC50 of L-OHP in the HCT-116 cells. Flow cytometric analysis showed that miR-218 overexpression alone promoted cell apoptosis in the HCT-116/L-OHP cells, which was further enhanced in response to L-OHP, and miR-218 inhibition decreased cell apoptosis in the HCT-116 cells following treatment with L-OHP. Western blot analysis indicated that, compared with the small increase observed in HCT-116 cells, the relative LC3 II level in HCT-116/L-OHP cells after lysosome inhibition via chloroquine (CQ) was markedly upregulated following L-OHP treatment, suggesting induction of autophagy. Exposure of HCT-116/L-OHP cells to L-OHP after control mimic transfection increased autophagic flux, as reflected by increased LC3 II levels, while miR-218 overexpression partly reversed L-OHP-mediated LC3 II accumulation. Additionally, both miR-218 overexpression and CQ treatment promoted L-OHP-induced HCT-116/L-OHP cell apoptosis. Molecularly, our results confirmed that miR-218 directly targets the YEATS4 gene and inhibits YEATS4 expression. Furthermore, YEATS4 overexpression without the 3'-untranslated region (3'-UTR) restored miR-218-inhibited YEATS4 and LC3 II expression, and abolished miR-218-stimulated cell viability loss and cell apoptosis increase in response to L-OHP. In conclusion, miR-218 sensitized HCT-116/L-OHP cells to L-OHP-induced cell apoptosis via inhibition of cytoprotective autophagy by targeting YEATS4 expression. AD - Department of Gastrointestinal Surgery, Tumor Hospital of Henan Province (The Affiliated Tumor Hospital of Zhengzhou University), Zhengzhou, Henan 450008, P.R. China Department of Medical Oncology, Zhengzhou Central Hospital (The Affiliated Central Hospital of Zhengzhou University), Zhengzhou, Henan 450007, P.R. China Department of Digestive Oncology, Tumor Hospital of Henan Province (The Affiliated Tumor Hospital of Zhengzhou University), Zhengzhou, Henan 450008, P.R. China AU - Fu,Qiang AU - Cheng,Jing AU - Zhang,Jindai AU - Zhang,Yonglei AU - Chen,Xiaobing AU - Xie,Jianguo AU - Luo,Suxia DA - 2016/12/01 DO - 10.3892/or.2016.5195 EP - 3690 IS - 6 JO - Oncol Rep KW - miR-218 YEATS4 colorectal cancer chemosensitivity autophagy cell apoptosis PY - 2016 SN - 1021-335X 1791-2431 SP - 3682 ST - Downregulation of YEATS4 by miR-218 sensitizes colorectal cancer cells to L-OHP-induced cell apoptosis by inhibiting cytoprotective autophagy T2 - Oncology Reports TI - Downregulation of YEATS4 by miR-218 sensitizes colorectal cancer cells to L-OHP-induced cell apoptosis by inhibiting cytoprotective autophagy UR - https://doi.org/10.3892/or.2016.5195 VL - 36 ER -