Du Guanghong, Yu Xuelian, Chen Yun, Cai Wangting
Department of Geriatrics, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
Organ transplant center, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
Front Oncol. 2021 Feb 26;11:634596. doi: 10.3389/fonc.2021.634596. eCollection 2021.
Colorectal cancer (CRC) is regarded as one of the most common malignancies in the world. MiR-1-3p was reported to be a tumor suppressor in CRC. However, the mechanisms have not been fully elucidated.
To identify CRC-associated miRNA, microarray data set GSE30454 was downloaded from the Gene Expression Omnibus database (GEO), and miR-1-3p was screened out as a candidate. The expression of miR-1-3p was detected using quantitative real-time polymerase chain reaction (qRT-PCR) in CRC cell lines and tissues. CCK-8 assay and transwell invasion assay were performed to determine CRC cell line proliferation and invasion, respectively. The levels of YWHAZ and EMT-associated proteins were detected using western blotting.
Bioinformatic analysis showed that miR-1-3p was downregulated in CRC tissues, which is verified by our experimental validation. The overexpression of miR-1-3p significantly suppressed CRC cell proliferation and invasion. Further studies showed that YWHAZ was a direct target of miR-1-3p and mediated epithelial-mesenchymal transition (EMT) modulated by miR-1-3p.
Our results demonstrated that miR-1-3p suppresses colorectal cancer cell proliferation and metastasis through regulating YWHAZ-mediated EMT, which may support a novel therapeutic strategy for CRC patients.
结直肠癌(CRC)被认为是世界上最常见的恶性肿瘤之一。据报道,miR-1-3p在结直肠癌中是一种肿瘤抑制因子。然而,其机制尚未完全阐明。
为了鉴定与结直肠癌相关的微小RNA(miRNA),从基因表达综合数据库(GEO)下载了微阵列数据集GSE30454,并筛选出miR-1-3p作为候选基因。使用定量实时聚合酶链反应(qRT-PCR)检测结直肠癌细胞系和组织中miR-1-3p的表达。分别进行CCK-8试验和Transwell侵袭试验以测定结直肠癌细胞系的增殖和侵袭能力。使用蛋白质印迹法检测YWHAZ和上皮-间质转化(EMT)相关蛋白的水平。
生物信息学分析表明,miR-1-3p在结直肠癌组织中表达下调,我们的实验验证证实了这一点。miR-1-3p的过表达显著抑制了结直肠癌细胞的增殖和侵袭。进一步研究表明,YWHAZ是miR-1-3p的直接靶标,并介导了miR-1-3p调节的上皮-间质转化(EMT)。
我们的结果表明,miR-1-3p通过调节YWHAZ介导的EMT抑制结直肠癌细胞的增殖和转移,这可能为结直肠癌患者提供一种新的治疗策略。