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

Autor: Xingyue Weng, Tao Ma, Qi Chen, Bryan Wei Chen, Jianzhen Shan, Wei Chen, Xiao Zhi
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Heliyon, Vol 10, Iss 5, Pp e27027- (2024)
Druh dokumentu: article
ISSN: 2405-8440
DOI: 10.1016/j.heliyon.2024.e27027
Popis: 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.
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