MicroRNA-193a-3p inhibits cell proliferation in prostate cancer by targeting cyclin D1.
MicroRNA-193a-3p inhibits cell proliferation in prostate cancer by targeting cyclin D1.
复制标题
DOI：
10.3892/ol.2017.6865
复制
发表时间：
2017-11
期刊：
影响因子：
2.9
通讯作者：
Xie L
中科院分区：
文献类型：
--
作者：
Liu Y;Xu X;Xu X;Li S;Liang Z;Hu Z;Wu J;Zhu Y;Jin X;Wang X;Lin Y;Chen H;Mao Y;Luo J;Zheng X;Xie L
MicroRNAs(MiRNAs)是一种小的非编码RNA，通过改变靶基因的表达来影响各种生物过程。此前的miRNA微阵列分析显示，与良性前列腺增生症组织相比，前列腺癌组织中miR-193a-3p的水平显著降低。然而，miR-193a-3p的作用尚未阐明。本研究采用逆转录定量聚合酶链式反应(RT-qPCR)检测miR-193a-3p在两株人前列腺癌细胞系中的表达水平。通过将Mimics导入DU-145和PC3细胞系，建立了miR-193a-3p的强制过表达。用细胞活力分析、流式细胞仪和集落形成实验检测细胞增殖和细胞周期。此外，通过荧光素酶活性测定、RT-qPCR和Western印迹分析确定了miR-193a-3p的目的基因。免疫印迹法检测miR-193a-3p对细胞周期的调节作用。结果表明，miR-193a-3p在前列腺癌细胞系中的表达水平低于RWPE正常前列腺上皮细胞系。随后的功能获得研究表明，稳定的miR-193a-3p转基因抑制了细胞的存活、增殖和集落形成，并诱导前列腺癌细胞G1期停滞。荧光素酶活性测定和免疫印迹分析表明，细胞周期蛋白D1(CCND1)是miR-193a-3p的直接靶基因。此外，CCND1的强制表达能够对抗miR-193a-3p在前列腺癌细胞中的抑制作用。综上所述，这些结果提示miR-193a-3p可能通过调节CCND1的表达抑制前列腺癌细胞的存活、增殖和存活，miR-193a-3p可能是前列腺癌治疗的一个新的生物标志物。
MicroRNAs (miRNAs) are small non-coding RNAs that affect various biological processes by altering the expression of a target gene. An miRNA microarray analysis has previously revealed a significant decrease in miR-193a-3p levels in prostate cancer tissues compared with that in their benign prostate hyperplasia counterparts. However, the role of miR-193a-3p has yet to be elucidated. In the present study, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to evaluate the expression levels of miR-193a-3p in two human prostate cancer cell lines. Forced overexpression of miR-193a-3p was established by transfecting mimics into DU-145 and PC3 cell lines. Cell proliferation and the cell cycle were assessed using a cell viability assay, flow cytometry and a colony formation assay. In addition, the target gene of miR-193a-3p was determined by a luciferase assay, RT-qPCR and western blot analysis. The regulation of the cell cycle by miR-193a-3p was also evaluated by western blotting. The results demonstrated that miR-193a-3p expression levels were lower in prostate cancer cell lines as compared with the RWPE normal prostate epithelium cell line. Subsequent gain-of-function studies revealed that stable miR-193a-3p transfection inhibited cell viability, proliferation and colony formation, and induced G1 phase arrest in prostate cancer cells. A luciferase assay and western blot analysis identified cyclin D1 (CCND1) as a direct target gene of miR-193a-3p. In addition, the forced expression of CCND1 was able to counter the inhibitory effects of miR-193a-3p transfection in the prostate cancer cells. In summary, the results suggest that miR-193a-3p may inhibit the viability, proliferation and survival of prostate cancer cells by regulating the expression profile of CCND1, and that miR-193a-3p may be a novel therapeutic biomarker for prostate cancer.
登录
查看更多内容
影响因子：
11.2
作者：
Lin PC;Chiu YL;Banerjee S;Park K;Mosquera JM;Giannopoulou E;Alves P;Tewari AK;Gerstein MB;Beltran H;Melnick AM;Elemento O;Demichelis F;Rubin MA
通讯作者：
Rubin MA
影响因子：
5.3
作者：
Wojcicka, A.;de la Chapelle, A.;Jazdzewski, K.
通讯作者：
Jazdzewski, K.
影响因子：
11.2
作者：
Li Z;Chen K;Jiao X;Wang C;Willmarth NE;Casimiro MC;Li W;Ju X;Kim SH;Lisanti MP;Katzenellenbogen JA;Pestell RG
通讯作者：
Pestell RG
影响因子：
64.8
作者：
Jirawatnotai S;Hu Y;Michowski W;Elias JE;Becks L;Bienvenu F;Zagozdzon A;Goswami T;Wang YE;Clark AB;Kunkel TA;van Harn T;Xia B;Correll M;Quackenbush J;Livingston DM;Gygi SP;Sicinski P
通讯作者：
Sicinski P
影响因子：
0.4
作者：
He, L.;Yao, H.;Hao, C. Q.
通讯作者：
Hao, C. Q.