title: MiR-221 expression affects invasion potential of human prostate carcinoma cell lines by targeting DVL2.
abstract: The aim of this study is to evaluate the effect of the variation of miR-221 on the prostate cancer cells' NE differentiation and invasive function and to examine the function of miR-221 in plasma as a blood-based miRNA biomarker candidate for CaP. The expression of 7 miRNAs in LNCaP, LNCaP-AI, and PC3 prostate cancer cell lines was detected by Northern blotting. LNCaP and LNCaP-AI cells cultured in androgen-depleted medium were transfected with different synthetic miRs. The ability of invasiveness was evaluated by a Matrigel invasion assay. Cell growth was assessed by using the CCK-8 cell proliferation assay at different times. The expression of NSE and DVL2 during the neuroendocrine phenotype and migration were measured by qRT-PCR and Western blot. The level of miR-221 in the prostate cancer samples was measured by qRT-PCR. MiR-221 was significantly increased compared AIPC with ADPC cell lines. Overexpression of miR-221 in LNCaP cells significantly increased the level of NSE expression and induced NE differentiation. Knocking down the level of miR-221 expression with antagonist miR-221 in the LNCaP-AI cell line increased migration and invasion (P < 0.01). DVL2 protein level was up-regulated after transfection of anti-miR-221. MiR-221 was up-regulated in CaP plasma (P < 0.01). We demonstrate a significant difference in miR-221 expression between ADPC and AIPC. MiR-221 may contribute to NE differentiation, which may be the cause for AIPC. We also suggest that miR-221 may control the migration of AIPC cells through DVL2, working as a key regulator in advanced CaP. The role of miR-221 in other target mRNA needs to be further investigated.
authors.affiliation: Department of Urology, General Hospital of Jinan Military Command, 25 Shifan Road, 250031 Jinan, China. doctorchangzheng@163.com
authors.forename: Chang
authors.initials: C
authors.lastname: Zheng
authors.forename: Sun
authors.initials: S
authors.lastname: Yinghao
authors.forename: Jiao
authors.initials: J
authors.lastname: Li
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000368:Aged; D000728:Androgens / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D015152:Blotting, Northern; D015153:Blotting, Western; D002448:Cell Adhesion; D002465:Cell Movement; D000072261:Dishevelled Proteins; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009376:Neoplasms, Hormone-Dependent / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D011467:Prostate / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D011944:Receptors, Androgen / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000728:Androgens; D014408:Biomarkers, Tumor; D000072261:Dishevelled Proteins; D035683:MicroRNAs; D010750:Phosphoproteins; D012333:RNA, Messenger; D011944:Receptors, Androgen; C000606581:DVL2 protein, human; C525709:MIR221, human