Liang Xuan, Li Hecheng, Fu Delai, Chong Tie, Wang Ziming, Li Zhaolun
Department of Oncology, The First Affiliated Hospital, Xi'an Jiaotong University Medical College, Xi'an, Shaanxi 710061, China.
Department of Urology, The Second Affiliated Hospital, Xi'an Jiaotong University Medical College, Xi'an, Shaanxi 710004, China.
Biochem Biophys Res Commun. 2016 Nov 11;480(2):208-214. doi: 10.1016/j.bbrc.2016.10.029. Epub 2016 Oct 13.
MicroRNAs (miRNAs) have been known to be implicated in tumorigenic programs. miR-1297 has been reported to be dysregulated and involved in cancer progression in many types of human cancers. However, the expression level and the role of miR-1297 in prostate cancer remain unclear. Herein, we aimed to investigate the potential role and molecular mechanism of miR-1297 in prostate cancer progression. We found that miR-1297 was significantly downregulated in human prostate cancer specimens as well as in several prostate cancer cell lines. In addition, functional experiments demonstrated that overexpression of miR-1297 remarkably inhibited prostate cancer cell proliferation and invasion whereas miR-1297 suppression significantly promoted prostate cancer cell proliferation and invasion. Bioinformatics analysis showed that the Astrocyte elevated gene-1 (AEG-1), a well-known oncogene, is a predicted target of miR-1297. Dual-luciferase reporter assay showed that miR-1297 was able to directly target the 3'-untranslated region of AEG-1. In addition, RT-qPCR and Western blot analysis showed that miR-1297 regulated the mRNA and protein expression levels of AEG-1. We also showed that miR-1297 was able to regulate the Wnt signaling pathway. Moreover, rescue assays indicated that AEG-1 contributed to miR-1297-endowed effects on cell proliferation and invasion as well as Wnt signaling pathway. Taken together, these findings suggest that miR-1297 inhibits prostate cancer proliferation and invasion by targeting AEG-1, thereby providing novel insight into understanding the pathogenesis of prostate cancer. Thus, miR-1297 may be a novel potential therapeutic candidate to treat prostate cancer.
微小RNA（miRNA）已被证实与肿瘤发生过程有关。据报道，miR-1297在多种人类癌症中表达失调，并参与癌症进展。然而，miR-1297在前列腺癌中的表达水平及其作用仍不清楚。在此，我们旨在研究miR-1297在前列腺癌进展中的潜在作用和分子机制。我们发现，miR-1297在人类前列腺癌标本以及几种前列腺癌细胞系中显著下调。此外，功能实验表明，miR-1297的过表达显著抑制前列腺癌细胞的增殖和侵袭，而miR-1297的抑制则显著促进前列腺癌细胞的增殖和侵袭。生物信息学分析表明，星形胶质细胞升高基因-1（AEG-1），一种著名的癌基因，是miR-1297的预测靶点。双荧光素酶报告基因检测表明，miR-1297能够直接靶向AEG-1的3'-非翻译区。此外，RT-qPCR和蛋白质印迹分析表明，miR-1297调节AEG-1的mRNA和蛋白质表达水平。我们还表明，miR-1297能够调节Wnt信号通路。此外，挽救实验表明，AEG-1有助于miR-1297对细胞增殖、侵袭以及Wnt信号通路产生的影响。综上所述，这些发现表明，miR-1297通过靶向AEG-1抑制前列腺癌的增殖和侵袭，从而为理解前列腺癌的发病机制提供了新的见解。因此，miR-1297可能是治疗前列腺癌的一种新型潜在治疗候选物。
