Tumor‐suppressive microRNA‐218 inhibits cancer cell migration and invasion via targeting of LASP1 in prostate cancer

Cancer Science

Rika Nishikawa¹  Yusuke Goto¹  Shinichi Sakamoto³  Takeshi Chiyomaru⁴  Hideki Enokida⁴  Satoko Kojima²  Takashi Kinoshita¹  Noriko Yamamoto¹  Masayuki Nakagawa⁴  Yukio Naya²  Tomohiko Ichikawa³ 

[1] Department of Functional Genomics, Chiba, Japan;Department of Urology, Teikyo University Chiba Medical Center, Chiba, Japan;Department of Urology, Chiba University Graduate School of Medicine, Chiba, Japan;Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan

关键词: LASP1;    microRNA;    miR‐218;    prostate cancer;    tumor suppressor;   

DOI  :  10.1111/cas.12441

来源: Wiley

【 摘 要 】

Abstract

Our recent studies of the microRNA (miRNA) expression signature in prostate cancer (PCa) indicated that miRNA-218 (miR-218) was significantly downregulated in clinical specimens, suggesting that miR-218 might act as a tumor-suppressive miRNA in PCa. The aim of the present study was to investigate the functional significance of miR-218 in PCa and to identify novel miR-218-regulated cancer pathways and target genes involved in PCa oncogenesis and metastasis. Restoration of miR-218 in PCa cell lines (PC3 and DU145) revealed that this miRNA significantly inhibited cancer cell migration and invasion. Gene expression data and in silico analysis demonstrated that LIM and SH3 protein 1 (LASP1) is a potential target of miR-218 regulation. LASP1 is a cytoskeletal scaffold protein that plays critical roles in cytoskeletal organization and cell migration. Luciferase reporter assays showed that miR-218 directly regulated expression of LASP1. Moreover, downregulating the LASP1 gene significantly inhibited cell migration and invasion in cancer cells, and the expression of LASP1 was upregulated in cancer tissues. We conclude that loss of tumor-suppressive miR-218 enhanced cancer cell migration and invasion in PCa through direct regulation of LASP1. Our data on pathways regulated by tumor-suppressive miR-218 provide new insight into the potential mechanisms of PCa oncogenesis and metastasis.

【 授权许可】

CC BY-NC-ND   
© 2014 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.