KSRP suppresses cell invasion and metastasis through miR-23a-mediated EGR3 mRNA degradation in non-small cell lung cancer

Ming Hsien Chien, Wei Jiunn Lee, Yi Chieh Yang, Yin Lin Li, Bo Rong Chen, Tsu Yao Cheng, Pei Wen Yang, Ming Yang Wang, Yi Hua Jan, Yen Kuang Lin, Jang Ming Lee, Michael Hsiao, Jin Shing Chen, Kuo Tai Hua

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

KH-type splicing regulatory protein (KSRP) is a single-strand RNA binding protein which regulates mRNA stability either by binding to AU-rich elements (AREs) of mRNA 3′UTR or by facilitating miRNA biogenesis to target mRNA. Unlike its well-characterized function at the molecular level in maintaining RNA homeostasis, the role of KSRP in cancer progression remains largely unknown. Here we investigate the role of KSRP in non-small cell lung cancer (NSCLC). We first examined KSRP expression by immunohistochemistry in a cohort containing 196 NSCLC patients and observed a strong positive correlation between KSRP expression and survival of NSCLC patients. Multivariate analysis further identified KSRP as an independent prognostic factor. Manipulating KSRP expression significantly affected in vitro cell mobility and in vivo metastatic ability of NSCLC cells. Microarray analysis identified an ARE-containing gene, EGR3, as a downstream effector of KSRP in NSCLC. Interestingly, we found that KSRP decreased EGR3 mRNA stability in an ARE-independent manner. By screening KSRP-regulated miRNAs in NSCLC cells, we further found that miR-23a directly binds to EGR3 3′UTR, reducing EGR3 expression and thereby inhibiting NSCLC cell mobility. Our findings implicate a targetable KSRP/miR-23a/EGR3 signaling axis in advanced tumor phenotypes.

Original languageEnglish
Pages (from-to)1013-1024
Number of pages12
JournalBiochimica et Biophysica Acta - Gene Regulatory Mechanisms
Volume1860
Issue number10
DOIs
Publication statusPublished - Oct 1 2017

Keywords

  • Cell invasion
  • KSRP
  • Metastasis
  • miRNA processing
  • mRNA decay

ASJC Scopus subject areas

  • Structural Biology
  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Genetics

Fingerprint Dive into the research topics of 'KSRP suppresses cell invasion and metastasis through miR-23a-mediated EGR3 mRNA degradation in non-small cell lung cancer'. Together they form a unique fingerprint.

  • Cite this

    Chien, M. H., Lee, W. J., Yang, Y. C., Li, Y. L., Chen, B. R., Cheng, T. Y., Yang, P. W., Wang, M. Y., Jan, Y. H., Lin, Y. K., Lee, J. M., Hsiao, M., Chen, J. S., & Hua, K. T. (2017). KSRP suppresses cell invasion and metastasis through miR-23a-mediated EGR3 mRNA degradation in non-small cell lung cancer. Biochimica et Biophysica Acta - Gene Regulatory Mechanisms, 1860(10), 1013-1024. https://doi.org/10.1016/j.bbagrm.2017.08.005