miR-202 inhibits growth, migration and invasion of oral squamous cell carcinoma cells by down-regulating NFATc3 / 中国肿瘤生物治疗杂志

@#[摘 要] 目的：探讨miR-202-5p对口腔鳞状细胞癌（oral squamous carcinoma，OSCC）细胞生长、集落形成、迁移和侵袭的影响及其可能的机制。方法：通过qPCR法检测OSCC细胞系（Tca8113和SCC-4）和口腔角质细胞HOK中miR-202-5p和T细胞核因子c3（nuclear factor of activated T-cells isoform c3，NFATc3）mRNA的表达水平；将miR-202-5p mimic或/和NFATc3过表达质粒转染入Tca8113和SCC-4细胞，用MTT和集落形成实验检测转染对细胞增殖的影响，划痕伤口愈合实验和Transwell实验检测转染对细胞迁移和侵袭的影响，用Western blotting实验检测转染对NFATc3蛋白表达的影响；通过双荧光素酶报告基因实验验证miR-202-5p对候选靶基因NFATc3的直接调控作用。结果：与正常口腔角质细胞HOK相比，miR-202-5p在OSCC细胞Tca8113和SCC-4中呈低表达（均P<0.01），NFATc3 mRNA和蛋白质表达显著升高（P<0.01）。在Tca8113细胞和SCC-4细胞中，过表达miR-202-5p可显著抑制细胞生长、集落形成、迁移、侵袭以及细胞中NFATc3表达（均P<0.01）。NFATc3被证实是miR-202-5p的靶基因，过表达NFATc3能逆转miR-202-5p对OSCC细胞生长、迁移和侵袭的抑制作用。结论：miR-202-5p通过下调NFATc3表达发挥其肿瘤抑制功能，导致OSCC细胞的生长、迁移和侵袭受到抑制。

Study on LncRNA SOX21-AS1 Affecting Biological Behavior of Colorectal Cancer Cells by Targeting MiR-202-5p / 胃肠病学

Background: Long non-coding RNA (lncRNA) could participate in the process of tumorigenesis by regulating the expression of miRNA, but the molecular mechanism of lncRNA in the development and metastasis of colorectal cancer has not been elucidated. Aims: To investigate the molecular mechanism of lncRNA SOX21-AS1 affecting the biological process of colorectal cancer cells by regulating the expression of microRNA-202-5p (miR-202-5p). Methods: The colorectal cancer HCT116 and SW480 cells were transfected with SOX21-AS1 small interfering RNA (si-SOX21-AS1), miR-202-5p mimics and its inhibitor. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the mRNA expressions of SOX21-AS1 and miR-202-5p. Cell proliferation was detected by MTT assay. Flow cytometry was used to detect cell apoptosis. Transwell experiments were used to detect cell migration and invasion. Dual luciferase reporter assay was used to validate the targeted regulatory relationship between SOX21-AS1 and miR-202-5p. Western blotting was used to detect the protein expressions of cyclin D1, MMP-2 and cleaved caspase-3. Results: The mRNA expression of SOX21-AS1 in colorectal cancer cells was significantly higher than that in normal colonic mucosal epithelial cells (P<0.05), while the mRNA expression of miR-202-5p was significantly decreased (P<0.05). Silencing SOX21-AS1 or up-regulating miR-202-5p significantly inhibited proliferation, migration and invasion of HCT116, SW480 cells, the cell apoptosis rate was significantly increased (P<0.05), and significantly inhibited the protein expressions of cyclin D1 and MMP-2 (P<0.05), however, the protein expression of cleaved caspase-3 was significantly increased (P<0.05). SOX21-AS1 could bind to miR-202-5p and negatively regulate the expression and activity of miR-202-5p. Inhibition of miR-202-5p expression reversed the effect of silencing SOX21-AS1 on proliferation, apoptosis, migration and invasion of colorectal cancer cells. Conclusions: Silencing SOX21-AS1 inhibits the proliferation, migration and invasion of colorectal cancer cells and induces cell apoptosis by up-regulating the expression of miR-202-5p.