K-homology splicing regulatory protein (KSRP) promotes post-transcriptional destabilization of Spry4 transcripts in non-small cell lung cancer

Rama Kamesh Bikkavilli, Sereke Adam Zerayesus, Michelle Van Scoyk, Lora Wilson, Pei Ying Wu, Abhinaya Baskaran, Ke Tang, Syed Raheem, Blain A. Samuelson, Narsa M. Reddy, Sekhar P. Reddy, Carlyne D. Cool, Beata Kosmider, Sreedevi Avasarala, Robert A. Winn*

*Corresponding author for this work

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

AU-rich element-binding proteins (ARE-BPs) offer posttranscriptional regulation of gene expression via physical interaction and recruitment of RNA decay machinery to the AU-rich elements within the 3′-UTR of the target transcripts. However, the role of ARE-BPs in lung cancer remains poorly understood. In this study, we have identified that K-homology splicing regulatory protein (KSRP), an ARE-BP, is robustly up-regulated in human lung cancer. Importantly, Kaplan-Meier survival analysis indicated that elevated KSRP expression was correlated with poor overall survival of lung cancer patients. Furthermore, cigarette smoke, a leading risk factor for lung cancer, was also identified to be an important contributor to increased KSRP expression. Remarkably, silencing of KSRP decreased cell proliferation, reversed anchorage-independent growth, and reduced migration/invasion, suggesting an oncogenic role for KSRP in lung cancer. Finally, we provide mechanistic evidence that KSRP promotes the down-regulation of Spry4 by a previously unidentified mechanism, i.e. post-transcriptional mRNA regulation.

Original languageEnglish (US)
Pages (from-to)7423-7434
Number of pages12
JournalJournal of Biological Chemistry
Volume292
Issue number18
DOIs
StatePublished - May 5 2017

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Bikkavilli, R. K., Zerayesus, S. A., Van Scoyk, M., Wilson, L., Wu, P. Y., Baskaran, A., Tang, K., Raheem, S., Samuelson, B. A., Reddy, N. M., Reddy, S. P., Cool, C. D., Kosmider, B., Avasarala, S., & Winn, R. A. (2017). K-homology splicing regulatory protein (KSRP) promotes post-transcriptional destabilization of Spry4 transcripts in non-small cell lung cancer. Journal of Biological Chemistry, 292(18), 7423-7434. https://doi.org/10.1074/jbc.M116.757906