Decreased expression of H19/miR-675 ameliorates hypoxia-induced oxaliplatin resistance in colorectal cancer

Xingyue Weng; Tao Ma; Qi Chen; Bryan Wei Chen; Jianzhen Shan; Wei Chen; Xiao Zhi

doi:10.1016/j.heliyon.2024.e27027

Decreased expression of H19/miR-675 ameliorates hypoxia-induced oxaliplatin resistance in colorectal cancer

Heliyon. 2024 Feb 28;10(5):e27027. doi: 10.1016/j.heliyon.2024.e27027. eCollection 2024 Mar 15.

Authors

Xingyue Weng¹, Tao Ma², Qi Chen², Bryan Wei Chen², Jianzhen Shan¹, Wei Chen³, Xiao Zhi²

Affiliations

¹ Department of Medical Oncology, The First Affiliated Hospital, Zhejiang University School of Medicine, No.79, Qingchun Road, Hangzhou, Zhejiang, 310003, China.
² Department of Hepatobiliary and Pancreatic Surgery and Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang University School of Medicine, No.79, Qingchun Road, Hangzhou, Zhejiang, 310003, China.
³ Cancer Institute of Integrated Traditional Chinese and Western Medicine, Zhejiang Academy of Traditional Chinese Medicine, Tongde Hospital of Zhejiang Province, Hangzhou, 310012, Zhejiang Province, China.

Abstract

Hypoxic microenvironment, a hallmark of solid tumors, contributes to chemoresistance, and long noncoding (lnc) RNAs are involved in hypoxia-induced drug resistance. However, the role of lncRNAs in hypoxic tumor chemotherapy resistance remains unclear. Here, we aimed to elucidate the effects of lncRNAs in hypoxia-mediated resistance in colorectal cancer (CRC), as well as the underlying mechanisms. The results indicated that the expression of lncRNA H19 was enhanced in hypoxia- or oxaliplatin-treated CRC cells; moreover, H19 contributed to drug resistance in CRC cells both in vitro and in vivo. Mechanistically, H19 was noted to act as a competitive endogenous RNA of miR-675-3p to regulate epithelial-mesenchymal transition (EMT). Notably, an miR-675-3p mimic could attenuate the effects of H19 deficiency in CRC cells with hypoxia-induced chemoresistance. In conclusion, H19 downregulation may counteract hypoxia-induced chemoresistance by sponging miR-675-3p to regulate EMT; as such, the H19/miR-675-3p axis might be a promising therapeutic target for drug resistance in CRC.