Abstract

Hepatoma-derived growth factor (HDGF) is commonly over-expressed and plays critical roles in the development and progression in a variety of cancers. It has previously been shown that HDGF is overregulated in prostate cancer cells compared to normal prostate cells, which is correlated with cellular migration and invasion of prostate cancer. Here, the molecular mechanisms of HDGF in prostate cancer is investigated. It is shown that HDGF knockdown reduces prostate cancer cellular migration and invasion in both androgen-sensitive LNCaP cells and androgen-insensitive DU145 and PC3 cells. Furthermore, Western blot analysis reveals that HDGF knockdown inhibits epithelial-mesenchymal transition (EMT) of prostate cancer cells by upregulation of protein E-cadherin and downregulation of proteins N-cadherin, Vimentin, Snail and Slug. In addition, mechanistic studies reveal that proteins MMP2 and MMP9 are down-regulated. In conclusion, our data suggested that HDGF knockdown inhibits cellular migration and invasion in vitro of prostate cancer via modulating epithelial-mesenchymal transition (EMT) signaling pathway, as well as MMP2 and MMP9 signaling pathway. These results supported that HDGF is a relevant protein in the progression of prostate cancer and may serve as a potentially therapeutic target for prostate cancer as well as its downstream targets.

Highlights

  • Prostate cancer (PCa) develops in the unique gland of the male reproductive system and becomes the most common malignancy in men, which leads to a detriment to men’s health

  • Relative Hepatoma-derived growth factor (HDGF) mRNA levels were inhibited by lentivirus-mediated short hairpin RNA (shRNA) interference in DU145, PC3 and LNCaP cells

  • We analyzed the HDGF mRNA levels in the selected cells by quantitative real time PCR analysis (Fig 1C). Results of this analysis showed that the relative levels of HDGF mRNA were suppressed in DU145, PC3 and LNCaP cells treated by lentivirus shRNA-HDGF compared with these cells treated by lentivirus shRNA-CTR or PBS

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Summary

Introduction

Prostate cancer (PCa) develops in the unique gland of the male reproductive system and becomes the most common malignancy in men, which leads to a detriment to men’s health. In 2015, PCa was ranked the second most frequently diagnosed cancer in males worldwide and the fifth leading cause of cancer deaths in the world [1]. Mechanisms of HDGF on prostate cancer cell migration and invasion. Focused Research and Development Program of Shandong Province (grant Nos: 2016GSF201171 and 2017GSF18130) (http://jihlx.sdstc.gov.cn/ STDPMS/GG/Default.aspx)

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