Downregulation of microRNA-23a suppresses prostate cancer metastasis by targeting the PAK6-LIMK1 signaling pathway

// Songwang Cai 1, * , Ruihan Chen 2, * , Xiaojuan Li 3 , Yi Cai 4 , Zhiqiang Ye 2 , Shigeng Li 2 , Jun Li 4 , Huaiqiu Huang 5 , Shubin Peng 4 , Jun Wang 4 , Yiran Tao 4 , Hongxing Huang 6 , Xinglai Wen 7 , Jianfeng Mo 7 , Zhupeng Deng 8 , Jian Wang 9 , Yangfan Zhang 4 , Xin Gao 4 , Xingqiao Wen 4 1 Department of Cardiothoracic Surgery, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China 2 Department of Emergency, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China 3 Department of Health Care, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China 4 Department of Urology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China 5 Department of Dermatology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China 6 Department of Urology, Zhongshan People's Hospital, Zhongshan City, Guangdong, China 7 Department of Urology, Qingyuan People's Hospital, Qingyuan City, Guangdong, China 8 Department of Urology, Taishan People's Hospital, Taishan City, Guangdong, China 9 Department of Urology, The First People's Hospital of Foshan City, Foshan City, Guangdong, China * These authors have contributed equally to this work Correspondence to: Xingqiao Wen, e-mail: wenxq@mail.sysu.edu.cn Keywords: microRNA, miR23a, prostate cancer, metastasis, cytoskeleton Received: August 12, 2014      Accepted: December 08, 2014      Published: February 24, 2015 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.