Abstract

Circular RNA DDX17 (circDDX17) has been demonstrated as a tumor suppressor in colorectal cancer. However, mechanisms underlying circDDX17 effects in cases of prostate cancer (PCa) are not well understood. Thus, herein, we determined measures of circDDX17 expression by use of the TCGA database. Expression of circDDX17 in prostate cancer-afflicted tissue samples was determined by qRT-PCR. Functionally, circDDX17 induced remarkable inhibition of cell colonizing ability, invasion, and epithelial-mesenchymal transition (EMT) progression in vitro. Mechanistically, dual-luciferase reporter assays, RNA immunoprecipitation, and RNA pull-down experiments helped verify interactions between circDDX17 and miR-346. Low expression of circDDX17 occurred in TCGA PCa samples. Furthermore, circDDX17 expression was downregulated significantly in PCa. These results suggested that circDDX17 suppressed PC cell mobility, proliferation, and invasion. Mechanistic experiments indicated that circDDX17 might serve as a ceRNA of miR-346 to relieve repressive effects of miR-346 upon phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP). LHPP expression itself was downregulated in TCGA PCa samples. Overall, our findings indicated that the circDDX17/miR-346/LHPP pathway inhibited the progression of prostate cancer and that circDDX17 may be a new potential therapeutic or diagnostic target for treating and diagnosing prostate cancer. As our study also demonstrated for the first time that LHPP might act as an anticancer gene in prostate cancer, the findings could have wide-ranging implications for the treatment of this affliction.

Highlights

  • Prostate cancer (PCa) is the most prevalent type of cancer afflicting males and contributes to huge societal burden for many countries [1]

  • Discussion circDDX17 was firstly reported as a tumor suppressor for colorectal cancer and in relation to silencing of circDDX17 such as to inhibit tumor metastasis [8]

  • We found that circDDX17 had a negative effect on PCa cell metastasis and epithelial-mesenchymal transition (EMT)

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Summary

Introduction

Prostate cancer (PCa) is the most prevalent type of cancer afflicting males and contributes to huge societal burden for many countries [1]. Exonic circRNAs are the most thoroughly researched of all types of circRNAs. One type of circRNA, circDDX17, was first reported to act as a tumor suppressor in examinations of samples afflicted by colorectal cancer [8]. The exact roles of circDDX17 and its influences upon the dynamics and mechanisms underlying PCa remain unknown. To date, the BioMed Research International roles underlying the influence upon the mechanisms and dynamics of LHPP in PCa are yet to be elucidated. We hypothesized that circDDX17 would play an oncogenic role in PCa by way of competing with miR-346 such as to enhance LHPP expression and subsequently repress PCa progression. We sought to examine if and expected that circDDX17 could be a potential diagnostic or therapeutic target for PCa patients

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