AUTHOR=Mao Yuanshen , Li Wenfeng , Hua Bao , Gu Xin , Pan Weixin , Chen Qi , Xu Bin , Lu Chao , Wang Zhong 

TITLE=Circular RNA_PDHX Promotes the Proliferation and Invasion of Prostate Cancer by Sponging MiR-378a-3p

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=8

YEAR=2021

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2020.602707

DOI=10.3389/fcell.2020.602707

ISSN=2296-634X

ABSTRACT=<p>The dysregulation of circular RNAs (circRNAs) is implicated in the pathogenesis of prostate cancer (PCa). However, the underlying mechanisms by which hsa_circ_0003768 (circPDHX) contributes to PCa remain elusive. The differentially expressed circRNAs between PCa and normal tissues were identified by Gene Expression Omnibus dataset. The association of circPDHX and miR-378a-3p expression with the clinicopathological parameters and prognosis in patients with PCa was analyzed by fluorescence <italic>in situ</italic> hybridization and The Cancer Genome Atlas dataset. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and Transwell assays as well as a xenograft tumor model were used to assess the role of circPDHX in PCa cells. circPDHX-specific binding with miR-378a-3p was validated by bioinformatic analysis, luciferase gene reporter, and RNA immunoprecipitation assays. As a result, we found that increased expression of circPDHX was associated with Gleason score (<italic>P</italic> = 0.001) and pathogenic T stage (<italic>P</italic> = 0.01) and acted as an independent prognostic factor of poor survival (<italic>P</italic> = 0.036) in patients with PCa. Knockdown of circPDHX inhibited cell proliferation and invasion <italic>in vitro</italic> and <italic>in vivo</italic>, but ectopic expression of circPDHX reversed these effects. Furthermore, circPDHX could sponge miR-378a-3p to promote cell proliferation, but miR-378a-3p counteracted circPDHX-induced cell proliferation and insulin-like growth factor 1 receptor (IGF1R) expression in PCa cells. In conclusion, our findings demonstrated that circPDHX facilitated the proliferation and invasion of PCa cells by sponging miR-378a-3p.</p>