Mou Yueyang, He Nabin, Su Mengyang, Zhong Zihua, Ma Jiayu, Liu Jianling, Cheng Xi'an, Dai Penggao
National Engineering Research Center for Miniaturized Detection Systems, School of Life Sciences, Northwest University Xi'an, Shaanxi Province, People's Republic of China.
Department of Respiratory, Tongchuan People's Hospital Tongchuan, Shaanxi Province, People's Republic of China.
Am J Transl Res. 2021 Jan 15;13(1):183-196. eCollection 2021.
Colorectal cancer (CRC) remains one of the deadliest diseases in the whole world. Cancer recurrence and chemotherapeutic drug resistance limit the overall survival rate of patients with CRC. This study aimed to discover the latent miRNAs and genes associated with oxaliplatin resistance in CRC cells. The study found that miR-1254 is upregulated in oxaliplatin-resistant CRC cell line HCT116-R compared with its parental cell line HCT116 by transcriptome sequencing and small RNA sequencing. Meanwhile, (multiple EGF-like domains 6) was downregulated in HCT116-R cells. Transient transfection of miR-1254 mimics significantly reduced cell apoptosis, increased HCT116 tolerance to oxaliplatin, and enhanced expression. Furthermore, transfection of miR-1254 inhibitor increased apoptosis, decreased HCT116-R tolerance to oxaliplatin, and reduced expression. In addition, transient transfection of Si enhanced HCT116 cell resistance to oxaliplatin and reduced cell apoptosis. In summary, is a latent functional target of miR-1254 in regulating oxaliplatin resistance and apoptosis in human CRC cells, suggesting a potential therapeutic target for CRC.
结直肠癌（CRC）仍然是全球最致命的疾病之一。癌症复发和化疗耐药性限制了CRC患者的总生存率。本研究旨在发现与CRC细胞中奥沙利铂耐药相关的潜在miRNA和基因。研究发现，通过转录组测序和小RNA测序，与亲代细胞系HCT116相比，miR-1254在奥沙利铂耐药的CRC细胞系HCT116-R中上调。同时，多表皮生长因子样结构域6（multiple EGF-like domains 6）在HCT116-R细胞中下调。瞬时转染miR-1254模拟物显著减少细胞凋亡，增加HCT116对奥沙利铂的耐受性，并增强多表皮生长因子样结构域6的表达。此外，转染miR-1254抑制剂增加凋亡，降低HCT116-R对奥沙利铂的耐受性，并降低多表皮生长因子样结构域6的表达。另外，瞬时转染Si增强了HCT116细胞对奥沙利铂的抗性并减少细胞凋亡。总之，多表皮生长因子样结构域6是miR-1254在调节人CRC细胞奥沙利铂耐药性和凋亡中的潜在功能靶点，提示其可能成为CRC的治疗靶点。
