Weng Xingyue, Ma Tao, Chen Qi, Chen Bryan Wei, Shan Jianzhen, Chen Wei, Zhi Xiao
Department of Medical Oncology, The First Affiliated Hospital, Zhejiang University School of Medicine, No.79, Qingchun Road, Hangzhou, Zhejiang, 310003, China.
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.
Heliyon. 2024 Feb 28;10(5):e27027. doi: 10.1016/j.heliyon.2024.e27027. eCollection 2024 Mar 15.
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.
缺氧微环境是实体瘤的一个标志，它会导致化疗耐药，而长链非编码（lnc）RNA参与缺氧诱导的耐药。然而，lncRNA在缺氧肿瘤化疗耐药中的作用仍不清楚。在这里，我们旨在阐明lncRNA在结直肠癌（CRC）缺氧介导的耐药中的作用及其潜在机制。结果表明，lncRNA H19在缺氧或奥沙利铂处理的CRC细胞中表达增强；此外，H19在体外和体内均促进CRC细胞的耐药。机制上，发现H19作为miR-675-3p的竞争性内源性RNA来调节上皮-间质转化（EMT）。值得注意的是，miR-675-3p模拟物可以减弱H19缺陷对具有缺氧诱导化疗耐药的CRC细胞的影响。总之，H19下调可能通过海绵化miR-675-3p来调节EMT，从而抵消缺氧诱导的化疗耐药；因此，H19/miR-675-3p轴可能是CRC耐药的一个有前景的治疗靶点。
