LncRNA UCA1 acts as a sponge of miR-204 to up-regulate CXCR4 expression and promote prostate cancer progression.

Chang He,Zhuifeng Guo,Liang Qin,Yang Sun,Jiawen Wu,Fan Yang,Xuwei Lu

doi:10.1042/bsr20181465

Chang He, Zhuifeng Guo + Show 5 more

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https://doi.org/10.1042/bsr20181465

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Journal: Bioscience reports	Publication Date: May 2, 2019
Citations: 33	License type: CC BY 4.0

Affiliation: Fudan University

Abstract

Prostate cancer (PCa) is a devastating malignant disease with a poor prognosis. The aim of current study is to investigate the role of lncRNA-urothelial carcinoma associated 1 (UCA1) in the progression of PCa. We evaluated the expression levels of UCA1 in a total of 16 benign prostatic hyperplasia tissues (BPH) and 40 PCa tissues, as well as PCa cells. The functional regulatory effects of UCA1 were investigated using a series of cell function approaches. Our data showed that UCA1 is frequently overexpressed in PCa tissues compared with BPH tissues (P<0.01). Moreover, the higher expression of UCA1 was observed in patients with Gleason score ≥8 (P<0.05). In consistent, we found the expression levels of UCA1 was higher in the PCa cell lines PC-3, LnCaP, and DU-145 than in the normal prostate epithelial cell line RWPE-1 (P<0.01). Functionally, we found knockdown of UCA1 in PC-3 significantly suppressed cell growth and invasion of PC-3, while overexpression of UCA1 in DU-145 cells promote cell growth and invasion. Mechanistically, UCA1 overexpression permitted activation of CXCR4 oncogenes through inhibition of miR-204 activity, as evidenced by the positive association of these two genes with UCA1 levels and inverse correlation with miR-204 expression in PCa tissues. Luciferase activity assay further confirmed the targetting relationship between UCA1 and miR-204, CXCR4, and miR-204. The up-regulation of UCA1 in PC-3 cells significantly impaired the inhibitory effect of miR-204 on CXCR4 expression. Taken together, our research revealed that UCA1 works as an oncogene by targetting miR-204. The UCA1-miR-204-CXCR4 regulatory network regulated the growth and metastasis of PCa, providing new insight in the management of patients with such malignancy.

Highlights

Prostate cancer (PCa) is the second most common malignancy and a major leading cause of cancer death amongst men worldwide [1]
The results clearly showed that the expression level of urothelial carcinoma associated 1 (UCA1) was higher in PCa tissues than in benign prostatic hyperplasia tissues (BPH) tissues (P
These findings indicated that UCA1 is up-regulated in PCa tissues and cell lines and may play an important role in the development of PCa

Summary

Introduction

Prostate cancer (PCa) is the second most common malignancy and a major leading cause of cancer death amongst men worldwide [1]. While there is considerable morbidity and mortality as a result of PCa, a significant population of men with PCa have indolent and slow growing disease that does not require intervention. The discovery of new molecular targets for PCa may help to understand the pathogenesis, prognosis, or treatment of PCa. LncRNAs, a class of noncoding RNAs with the length ranging from 200 nts to almost 100 kilobases, play vital roles in cancer development [4]. Accumulating evidences showed that dysregulation of lncRNA expression attributes a tumor-suppressor or an oncogenic role to lncRNAs affecting

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