Department of Urology, Affiliated Weihai Second Municipal Hospital of Qingdao University, Weihai 264200, China.
J Nanosci Nanotechnol. 2019 Dec 1;19(12):7526-7531. doi: 10.1166/jnn.2019.16413.
Prostate cancer is one of the most common malignancy among men, previous reports suggest that microRNA regulates prostate cancer progression. In present study, we found a novel miRNA, miR-3648, was to be overexpressed in prostate cancer tissues. Its overexpression promoted proliferation of the prostate cancer cell line, LNCaP, as determined by MTT, colony formation and soft agar growth assays. Consistently, knockdown of miR-3648 inhibited LNCaP proliferation. The tumor suppressor, adenomatous polyposis coli 2 (APC2), which negatively regulates the Wnt/-catenin pathway, was the target of miR-3648. The results of the luciferase reporter assay suggested that miR-3648 binds directly to the 3'UTR of APC2. The Wnt/-catenin pathway promotes G1/S transition. We evaluated whether miR-3648 regulated the expression of key regulatory proteins involved in G1/S transition, and found that miR-3648 promoted cyclin D1 and cyclin E1 expression while inhibiting p21 expression. This suggested that miR-3648 promoted LNCaP proliferation by targeting APC2, which in turn activates the Wnt/-catenin pathway to produce the observed effects on cyclin D1, cyclin E1 and p21 expression. Moreover, there was a negative correlation between miR-3648 and APC2 expression in prostate cancer tissues.
前列腺癌是男性中最常见的恶性肿瘤之一，先前的报告表明 microRNA 调节前列腺癌的进展。在本研究中，我们发现一种新的 microRNA，miR-3648，在前列腺癌组织中过表达。其过表达通过 MTT、集落形成和软琼脂生长测定促进前列腺癌细胞系 LNCaP 的增殖。一致地，miR-3648 的敲低抑制了 LNCaP 的增殖。腺瘤性结肠息肉病基因 2 (APC2)，其负调节 Wnt/-连环蛋白途径，是 miR-3648 的靶标。荧光素酶报告基因测定的结果表明，miR-3648 直接结合 APC2 的 3'UTR。Wnt/-连环蛋白途径促进 G1/S 期过渡。我们评估了 miR-3648 是否调节 G1/S 期过渡中涉及的关键调节蛋白的表达，发现 miR-3648 促进了细胞周期蛋白 D1 和细胞周期蛋白 E1 的表达，同时抑制了 p21 的表达。这表明 miR-3648 通过靶向 APC2 促进 LNCaP 的增殖，从而激活 Wnt/-连环蛋白途径，对细胞周期蛋白 D1、细胞周期蛋白 E1 和 p21 的表达产生观察到的影响。此外，在前列腺癌组织中，miR-3648 与 APC2 的表达呈负相关。
