title: MicroRNA-21 directly targets MARCKS and promotes apoptosis resistance and invasion in prostate cancer cells.
abstract: Prostate cancer is one of the most common malignant cancers in men. Recent studies have shown that microRNA-21 (miR-21) is overexpressed in various types of cancers including prostate cancer. Studies on glioma, colon cancer cells, hepatocellular cancer cells and breast cancer cells have indicated that miR-21 is involved in tumor growth, invasion and metastasis. However, the roles of miR-21 in prostate cancer are poorly understood. In this study, the effects of miR-21 on prostate cancer cell proliferation, apoptosis, and invasion were examined. In addition, the targets of miR-21 were identified by a reported RISC-coimmunoprecipitation-based biochemical method. Inactivation of miR-21 by antisense oligonucleotides in androgen-independent prostate cancer cell lines DU145 and PC-3 resulted in sensitivity to apoptosis and inhibition of cell motility and invasion, whereas cell proliferation were not affected. We identified myristoylated alanine-rich protein kinase c substrate (MARCKS), which plays key roles in cell motility, as a new target in prostate cancer cells. Our data suggested that miR-21 could promote apoptosis resistance, motility, and invasion in prostate cancer cells and these effects of miR-21 may be partly due to its regulation of PDCD4, TPM1, and MARCKS. Gene therapy using miR-21 inhibition strategy may therefore be useful as a prostate cancer therapy.
authors.affiliation: Department of Urology, Ren Ji Hospital, Shanghai Jiao Tong University, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Li
authors.forename: Dong
authors.initials: D
authors.lastname: Li
authors.forename: Jianjun
authors.initials: J
authors.lastname: Sha
authors.forename: Peng
authors.initials: P
authors.lastname: Sun
authors.forename: Yiran
authors.initials: Y
authors.lastname: Huang
mesh_terms: D017209:Apoptosis / Q000235:genetics*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D015316:Genetic Therapy; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D035683:MicroRNAs / Q000378:metabolism*; D000076250:Myristoylated Alanine-Rich C Kinase Substrate; D009361:Neoplasm Invasiveness; D011471:Prostatic Neoplasms / Q000473:pathology* / Q000628:therapy
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C000619710:MARCKS protein, human; C524940:MIRN21 microRNA, human; D008565:Membrane Proteins; D035683:MicroRNAs; D000076250:Myristoylated Alanine-Rich C Kinase Substrate