Yang Dengke, Du Guang, Xu An, Xi Xuetao, Li Dong
Department of Urinary Surgery, Tongren Hospital, Shanghai Jiaotong University School of MedicineShanghai, PR China.
Am J Cancer Res. 2017 Nov 1;7(11):2209-2219. eCollection 2017.
MicroRNAs play key roles during various crucial cell processes, such as proliferation, migration, and invasion. In addition, microRNAs have been shown to possess oncogenic and tumor suppressive functions in human cancers. Increasing evidence has clarified that miR-149-3p, a novel cancer-related microRNA, plays an important role in suppression of proliferation, migration, and invasion; however, the effect and mechanisms underlying the miR-149-3p effect in bladder cancer (BCa) remain unclear. In the current study we found that the increased expression of miR-149-3p significantly suppressed cell proliferation, migration, and invasion ability in BCa. The suppressive effect was related to S100A4. A further investigation showed that miR-149-3p negatively regulated S100A4, as verified by the luciferase reporter assay. Furthermore, our study showed that S100A4 mediated the anti-metastatic effects of miR-149-3p on proliferation, migration, and invasion of BCa cells. Analysis of a xenograft mouse model showed that miR-149-3p expression significantly decreased tumor growth by targeting S100A4. Taken together, these data indicate that S100A4 promotes cell growth, migration, and invasion and can by reversed by miR-149-3p in BCa.
微小RNA在各种关键细胞过程中发挥着关键作用,如增殖、迁移和侵袭。此外,微小RNA在人类癌症中已显示出具有致癌和肿瘤抑制功能。越来越多的证据表明,miR-149-3p作为一种新型的癌症相关微小RNA,在抑制增殖、迁移和侵袭方面发挥重要作用;然而,miR-149-3p在膀胱癌(BCa)中的作用及潜在机制仍不清楚。在本研究中,我们发现miR-149-3p表达增加显著抑制了BCa细胞的增殖、迁移和侵袭能力。这种抑制作用与S100A4有关。进一步研究表明,miR-149-3p负向调节S100A4,荧光素酶报告基因检测证实了这一点。此外,我们的研究表明,S100A4介导了miR-149-3p对BCa细胞增殖、迁移和侵袭的抗转移作用。对异种移植小鼠模型的分析表明,miR-149-3p通过靶向S100A4显著降低肿瘤生长。综上所述,这些数据表明S100A4促进细胞生长、迁移和侵袭,而在BCa中miR-149-3p可逆转这种作用。