title: Downregulation of microRNA-23a suppresses prostate cancer metastasis by targeting the PAK6-LIMK1 signaling pathway.
abstract: Here we found that levels of miR-23a were decreased in prostate cancer cell lines and tumor tissues. These low levels were associated with poor patients' prognosis. MiR-23a inhibited migration and invasion of prostate cancer in vivo and in orthotopic prostate cancer mice model. MiR-23a decreased levels of p21-activated kinase 6 (PAK6). Expression of miR-23a inhibited phosphorylation of LIM kinase 1 (LIMK1) and cofilin, in turn suppressing formation of stress fibers and actin filaments, which was required for cell motility and invasion. PAK6 bound to LIMK1 and activated it via phosphorylation at Thr-508. Also, PAK6 and LIMK1 were colocalized in the cytoplasma. Thus, miR-23a regulated cytoskeleton by affecting LIMK1 and cofilin. In summary, we have identified the miR-23a-PAK6-LIMK1 pathway of prostate cancer metastasis. Potential therapeutic approach by targeting miR-23 is suggested.
authors.affiliation: Department of Cardiothoracic Surgery, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Songwang
authors.initials: S
authors.lastname: Cai
authors.affiliation: Department of Emergency, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Ruihan
authors.initials: R
authors.lastname: Chen
authors.affiliation: Department of Health Care, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Urology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Cai
authors.affiliation: Department of Emergency, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Ye
authors.affiliation: Department of Emergency, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Shigeng
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Urology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Dermatology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Huaiqiu
authors.initials: H
authors.lastname: Huang
authors.affiliation: Department of Urology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Shubin
authors.initials: S
authors.lastname: Peng
authors.affiliation: Department of Urology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Urology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Yiran
authors.initials: Y
authors.lastname: Tao
authors.affiliation: Department of Urology, Zhongshan People's Hospital, Zhongshan City, Guangdong, China.
authors.forename: Hongxing
authors.initials: H
authors.lastname: Huang
authors.affiliation: Department of Urology, Qingyuan People's Hospital, Qingyuan City, Guangdong, China.
authors.forename: Xinglai
authors.initials: X
authors.lastname: Wen
authors.affiliation: Department of Urology, Qingyuan People's Hospital, Qingyuan City, Guangdong, China.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Mo
authors.affiliation: Department of Urology, Taishan People's Hospital, Taishan City, Guangdong, China.
authors.forename: Zhupeng
authors.initials: Z
authors.lastname: Deng
authors.affiliation: Department of Urology, The First People's Hospital of Foshan City, Foshan City, Guangdong, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Urology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Yangfan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Urology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Gao
authors.affiliation: Department of Urology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Xingqiao
authors.initials: X
authors.lastname: Wen
mesh_terms: D000368:Aged; D000818:Animals; D045744:Cell Line, Tumor; D015536:Down-Regulation; D020869:Gene Expression Profiling; D057809:HEK293 Cells; D064593:Heterografts; D006801:Humans; D054461:Lim Kinases / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009362:Neoplasm Metastasis; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D015398:Signal Transduction; D054462:p21-Activated Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D035683:MicroRNAs; C534062:Mirn23b microRNA, mouse; C515892:LIMK1 protein, human; D054461:Lim Kinases; C429007:PAK6 protein, human; D054462:p21-Activated Kinases