Downregulation of microRNA-23a suppresses prostate cancer metastasis by targeting the PAK6-LIMK1 signaling pathway
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Songwang Cai1,*, Ruihan Chen2,*, Xiaojuan Li3, Yi Cai4, Zhiqiang Ye2, Shigeng Li2, Jun Li4, Huaiqiu Huang5, Shubin Peng4, Jun Wang4, Yiran Tao4, Hongxing Huang6, Xinglai Wen7, Jianfeng Mo7, Zhupeng Deng8, Jian Wang9, Yangfan Zhang4, Xin Gao4, Xingqiao Wen4
1Department of Cardiothoracic Surgery, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
2Department of Emergency, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
3Department of Health Care, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
4Department of Urology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
5Department of Dermatology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
6Department of Urology, Zhongshan People's Hospital, Zhongshan City, Guangdong, China
7Department of Urology, Qingyuan People's Hospital, Qingyuan City, Guangdong, China
8Department of Urology, Taishan People's Hospital, Taishan City, Guangdong, China
9Department of Urology, The First People's Hospital of Foshan City, Foshan City, Guangdong, China
*These authors have contributed equally to this work
Xingqiao Wen, e-mail: [email protected]
Keywords: microRNA, miR23a, prostate cancer, metastasis, cytoskeleton
Received: August 12, 2014 Accepted: December 08, 2014 Published: February 24, 2015
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.
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