Sun Dan, Li Tianren, Xin Haotian, An Jun, Yang Jieping, Lin Jiaxing, Meng Xin, Wang Biao, Ozaki Toshinori, Yu Meng, Zhu Yuyan
Department of Urology, The First Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China.
Department of Gynecology, The First Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China.
Oncol Lett. 2020 Oct;20(4):8. doi: 10.3892/ol.2020.11869. Epub 2020 Jul 15.
Since human bladder cancer (BC) is a common malignancy of the urinary system with poor prognosis, it is crucial to clarify the molecular mechanisms of BC development and progression. To the best of our knowledge, the current study demonstrated for the first time that miR-489-3p suppressed BC cell-derived tumor growth via the downregulation of histone deacetylase 2 (HDAC2). According to the results, expression levels of miR-489-3p were lower in BC tissues compared with corresponding normal tissues. Expression of miR-489-3p mimics in BC-derived T24 and 5637 cells resulted in a significant reduction in proliferation and migration rates. Furthermore, bioinformatics analyses indicated that HDAC2 may be a potential downstream target of miR-489-3p. In contrast to miR-489-3p, HDAC2 was expressed at higher levels in BC tissues compared with corresponding normal tissues. Additionally, small interfering RNA-mediated knockdown of HDAC2 caused a marked decrease in the proliferation and migration rates of T24 and 5637 cells. Consistent with these observations, expression of miR-489-3p mimics attenuated the growth of xenograft tumors arising from T24 cells and resulted in HDAC2 downregulation. In conclusion, the results of the current study indicated that the miR-489-3p/HDAC2 axis serves a role in the development and/or the progression of BC and may be a potential molecular target for the development of a novel strategy to treat patients with BC.
由于人类膀胱癌（BC）是泌尿系统常见的恶性肿瘤，预后较差，因此阐明BC发生发展的分子机制至关重要。据我们所知，当前研究首次证明miR-489-3p通过下调组蛋白去乙酰化酶2（HDAC2）抑制BC细胞衍生的肿瘤生长。结果显示，与相应正常组织相比，BC组织中miR-489-3p的表达水平较低。在源自BC的T24和5637细胞中表达miR-489-3p模拟物导致增殖和迁移率显著降低。此外，生物信息学分析表明HDAC2可能是miR-489-3p的潜在下游靶点。与miR-489-3p相反，与相应正常组织相比，HDAC2在BC组织中的表达水平较高。此外，小干扰RNA介导的HDAC2敲低导致T24和5637细胞的增殖和迁移率显著降低。与这些观察结果一致，miR-489-3p模拟物的表达减弱了源自T24细胞的异种移植肿瘤的生长，并导致HDAC2下调。总之，当前研究结果表明miR-489-3p/HDAC2轴在BC的发生和/或发展中起作用，可能是开发治疗BC患者新策略的潜在分子靶点。
