PUM1 represses CDKN1B translation and contributes to prostate cancer progression
Xin Li, Jian Yang, Xia Chen, Dandan Cao, Eugene Yujun Xu
Abstract
Posttranscriptional regulation of cancer gene expression programs plays a vital role in carcinogenesis; identifying the critical regulators of tumorigenesis and their molecular targets may provide novel strategies for cancer diagnosis and therapeutics. Highly conserved RNA-binding protein Pumilio-1 (PUM1) regulates mouse growth and cell proliferation, propelling us to examine its role in cancer. We found human <i>PUM1</i> is highly expressed in a diverse group of cancer, including prostate cancer; enhanced PUM1 expression is also correlated with reduced survival among prostate cancer patients. Detailed expression analysis in twenty prostate cancer tissues showed enhanced expression of <i>PUM1</i> at mRNA and protein levels. Knockdown of <i>PUM1</i> reduced prostate cancer cell proliferation and colony formation, and subcutaneous injection of <i>PUM1</i> knockdown cells led to reduced tumor size. Downregulation of PUM1 in prostate cancer cells consistently elevated cyclin-dependent kinase inhibitor 1B (CDKN1B) protein expression through increased translation but did not impact its mRNA level, while overexpression of PUM1 reduced CDKN1B protein level. Our finding established a critical role of PUM1 mediated translational control, particularly the PUM1-CDKN1B axis, in prostate cancer cell growth and tumorigenesis. We proposed that PUM1-CDKN1B regulatory axis may represent a novel mechanism for the loss of CDKN1B protein expression in diverse cancers and potential targets for therapeutics development.