General Surgery Department, Yidu Central Hospital of Weifang, 4138 Linglongshan Nanlu, Qingzhou, 262500, Shandong, China.
Mol Genet Genomics. 2018 Oct;293(5):1245-1253. doi: 10.1007/s00438-018-1457-y. Epub 2018 Jun 9.
MicroRNAs (miRNAs) are a novel class of diagnostic and therapeutic target in cancer. Here, we aimed to explore the effects and mechanism of miR-195 regulation in colon cancer. The expressions of several putative miRNAs in colon tumors, compared to those in normal tissues, were investigated by bioinformatical analysis of a Gene Expression Omnibus database. Quantitative real-time PCR analysis (qRT-PCR) was used to validate the identified changes in normal tissues, primary tumors, and metastatic tumors. MTT, soft agar colony formation, and transwell assays were used to evaluate the effects of miR-195 overexpression or inhibition on cell viability, proliferation, migration, and invasion. Targets of miR-195 were identified by TargetScan, and subsequently verified by qRT-PCR and Western blot. The role of miR-195 in the β-catenin pathway was also studied using RT-PCR and Western blot. MiR-195 expression was downregulated in colon carcinoma tissues and negatively correlated with the metastatic potential. While transfecting miR-195 mimics decreased the proliferation, migration, and invasion of colon cancer cells, miR-195 inhibition exerted opposing effects. WNT3A was identified as a direct target of miR-195. β-catenin was also downregulated by miR-195 in colon cancers. MiR-195 downregulation is associated with the enhanced proliferation, migration, and invasion of colon cancer. MiR-195 directly downregulates WNT3A. Our results indicate that miR-195 is a potential diagnostic marker and therapeutic target for improving the clinical management of colon cancer.
MicroRNAs (miRNAs) 是癌症诊断和治疗的新靶标。在这里,我们旨在探索 miR-195 调节在结肠癌中的作用和机制。通过基因表达综合数据库的生物信息学分析,研究了结肠癌肿瘤与正常组织中几种推定 miRNA 的表达情况。定量实时 PCR 分析 (qRT-PCR) 用于验证正常组织、原发性肿瘤和转移性肿瘤中鉴定出的变化。MTT、软琼脂集落形成和 Transwell 测定用于评估 miR-195 过表达或抑制对细胞活力、增殖、迁移和侵袭的影响。通过 TargetScan 鉴定 miR-195 的靶标,并通过 qRT-PCR 和 Western blot 进一步验证。还使用 RT-PCR 和 Western blot 研究了 miR-195 在 β-catenin 通路中的作用。miR-195 在结肠癌组织中表达下调,与转移潜能呈负相关。转染 miR-195 模拟物可降低结肠癌细胞的增殖、迁移和侵袭,而 miR-195 抑制则产生相反的效果。WNT3A 被鉴定为 miR-195 的直接靶标。β-catenin 也在结肠癌中被 miR-195 下调。miR-195 的下调与结肠癌增殖、迁移和侵袭的增强有关。miR-195 直接下调 WNT3A。我们的研究结果表明,miR-195 是改善结肠癌临床管理的潜在诊断标志物和治疗靶标。