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目的:探讨miR-598在结直肠癌转移中的作用和分子机制,为寻找新的结直肠癌治疗靶标提供理论依据。方法:收集30对人结直肠癌及癌旁正常组织标本,采用qRT-PCR检测miR-598的表达,采用Transwell和划痕实验确定miR-598对结直肠癌细胞侵袭和迁移能力的影响,利用在线靶基因预测软件,筛选出miR-598可能的下游靶基因Jagged 1(JAG1),利用Western blot及双荧光素酶报告基因实验检测miR-598对JAG1及上皮间质转化标志物(Vimentin及E-cadherin)表达的影响。结果:与正常肠黏膜组织对比,miR-598在结直肠癌组织中的表达水平明显降低;miR-598显著抑制结直肠癌细胞的侵袭及迁移能力;分子机制分析证实miR-598能够作用于JAG1的3’-UTR并抑制其表达;过表达miR-598显著下调Vimentin的表达水平,而提高E-cadherin的表达水平。结论:miR-598在人结直肠癌中表达明显下调;miR-598通过靶向调控靶基因JAG1的表达,抑制结直肠癌细胞EMT,从而有效的抑制了结直肠癌细胞的侵袭和迁移。
Objective: To investigate the role and molecular mechanism of miR-598 in the metastasis of colorectal cancer and to provide a theoretical basis for finding a new therapeutic target for colorectal cancer. Methods: Thirty specimens of human colorectal cancer and adjacent normal tissues were collected. The expression of miR-598 was detected by qRT-PCR. The effects of miR-598 on invasion and migration of colorectal cancer cells were determined by Transwell and scratch assay. (JAG1), a potential downstream target of miR-598, was screened by online target gene prediction software. Western blot and dual luciferase reporter assay were used to detect the effect of miR-598 on JAG1 and Vimentin and E -cadherin expression. Results: Compared with normal mucosa, the expression of miR-598 was significantly decreased in colorectal cancer tissues. MiR-598 significantly inhibited the invasion and migration of colorectal cancer cells. The molecular mechanism confirmed that miR-598 could act on JAG1 3’-UTR and inhibit its expression. Over-expression of miR-598 significantly down-regulated the expression of Vimentin and increased the expression of E-cadherin. Conclusion: miR-598 is significantly downregulated in human colorectal cancer. MiR-598 inhibits the invasion and metastasis of colorectal cancer cells by targeting the target gene JAG1 and inhibiting the EMT of colorectal cancer cells.