title: Norcantharidin induces autophagy-related prostate cancer cell death through Beclin-1 upregulation by miR-129-5p suppression.
abstract: Norcantharidin (NCTD) has an anticancer potential to allow it to be used in the treatment of some malignant cancers. However, whether NCTD may have similar anticancer effects on prostate cancer (PC) is unknown. Here, we aimed to examine the effects of NCTD on PC cells and the underlying mechanisms. We found that NCTD dose-dependently inhibited the PC cell growth, in either a cell counting kit-8 (CCK-8) assay or a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Moreover, NCTD dose-dependently increased the PC cell autophagy, through upregulation of Beclin-1. Furthermore, the Beclin-1 protein, but not mRNA, was regulated by NCTD in PC cells, suggesting post-transcriptional control of Beclin-1 by NCTD. Finally, microRNA (miR)-129-5p was found to be regulated by NCTD, and bioinformatics analyses showed that miR-129-5p targeted the 3'-UTR of Beclin-1 mRNA to inhibit its translation, which was confirmed by luciferase reporter assay. Together, these data suggest that NCTD may upregulate Beclin-1 through suppression of miR-129-5p to induce autophagic cell death and cell proliferation arrest in PC cells. Our study sheds light on using NCTD as a novel treatment for PC.
authors.affiliation: Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Xiao
authors.affiliation: Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Dai
authors.affiliation: Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China. dwyeli@163.com.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China. dwyeli@163.com.
authors.forename: Dingwei
authors.initials: D
authors.lastname: Ye
keywords: Autophagy; Beclin-1; Norcantharidin (NCTD); Prostate cancer (PC); miR-129-5p