title: IL-6 Inhibits the Targeted Modulation of PDCD4 by miR-21 in Prostate Cancer.
abstract: Prostate cancer is the most common cancer among men in the Unites States. The cytokine IL-6 activates several prostate cancer pathways, but its upstream trans-signaling pathway remains poorly understood. In this study, we evaluated the role of IL-6 in PDCD4 gene expression and how the microRNA miR-21 regulates this process in prostate cancer cell lines PC-3 and LNCaP. The expression pattern of PDCD4 from samples from human prostate cancer, precancerous lesions, and benign prostatic hyperplasia was investigated by immunohistochemistry. PDCD4 transcription and translation were detected by quantitative real-time PCR (qRT-PCR) and Western blot analysis, respectively. The targeted modulation of PDCD4 by miR-21 was analyzed in PC-3 and LNCaP cells, and the effect of IL-6 on the expression of PDCD4 was studied in vitro. PDCD4 expression in samples from the 3 tissue types progressively increased, and the expression levels of PDCD4 and prostate-specific antigen were negatively correlated. The levels of PDCD4 mRNA and protein in PC-3 and LNCaP cells transfected with anti-miR-21 constructs were lower than those in control cells. The expression of PDCD4 was inhibited by IL-6, but this effect was weakened in cell lines with low expression of miR-21. Our study demonstrates that the regulation of PDCD4 by miR-21 is targeted and IL-6 inhibits expression of the PDCD4 gene in PC-3 and LNCaP cells through the targeted function of miR-21 on PDCD4. These findings support the feasibility of future efforts for diagnosis and gene therapy for prostate cancer that are based on IL-6, miR-21, and PDCD4.
authors.affiliation: Department of Urology, the Second Hospital of Kunming Medical University, Kunming, Yunnan, China; Urology Institute of Yunnan Province, Kunming, Yunnan, China.
authors.forename: Biao
authors.initials: B
authors.lastname: Dong
authors.affiliation: The Emergency Center of The General Hospital of Jinan Military Region, Jinan, Shandong, China.
authors.forename: Zhihao
authors.initials: Z
authors.lastname: Shi
authors.affiliation: Department of Urology, the Second Hospital of Kunming Medical University, Kunming, Yunnan, China.
authors.forename: Jiaping
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Biochemistry, The Primary Medical College of Kunming Medical University, Kunming, Yunnan, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wu
authors.affiliation: Institute of Medical Biology, Chinese Academy of Medical Science &Peking Union Medical University, Kunming, Yunnan, China.
authors.forename: Zhaoqing
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Urology, the Second Hospital of Kunming Medical University, Kunming, Yunnan, China; Urology Institute of Yunnan Province, Kunming, Yunnan, China.
authors.forename: Kewei
authors.initials: K
authors.lastname: Fang
mesh_terms: D051017:Apoptosis Regulatory Proteins / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology*; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D017430:Prostate-Specific Antigen / Q000378:metabolism; D011470:Prostatic Hyperplasia / Q000378:metabolism / Q000473:pathology; D019048:Prostatic Intraepithelial Neoplasia / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D014162:Transfection
chemical_list: D051017:Apoptosis Regulatory Proteins; D015850:Interleukin-6; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; C114487:PDCD4 protein, human; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D017430:Prostate-Specific Antigen