The Significance of Circular RNA DDX17 in Prostate Cancer

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.

WGCNA Analysis Identifies Polycystic Ovary Syndrome-Associated Circular RNAs That Interact with RNA-Binding Proteins and Sponge miRNAs

“…Many studies have found that circRNAs contain miRNA response element and they could work as endogenous miRNA ‘sponges’ to bind to miRNAs and then exert negative regulation on the expression of downstream genes. circDDX17 was implicated to regulate miR-605-cell cycle-related factors (cyclin dependent kinase 1 and p21), 27 miR-346/phospholysine phosphohistidine inorganic pyrophosphate phosphatase, 36 miR-31-5p-KN motif and ankyrin repeat domains1 28 axes. Mechanistically, circ-ELF2 acted as a ceRNA for miR-510-5p to positively modulate the expression of mucin 15 at posttranscriptional level.…”

Circular RNAs in prostate cancer: Biogenesis, biological functions, and clinical significance

“… 65 2019 circDDX17 hsa_circ_0063308 down miR-346 LHPP inhibited cell proliferation, invasion, and EMT 20 pairs of PCa tissues and adjacent normal tissues; 22Rv1 and PC-3 cell lines Lin et al. 99 2020 circCRKL hsa_circ_0001206 down miR-141 KLF5 repressed cell cycle, migration, and invasion, and boosted apoptosis 45 pairs of PCa tissues and adjacent normal tissues; LNCaP, DU145, C4-2, 22RV1, and RWPE-1 cell lines Nan et al. 100 2020 hsa_circ_0007494 hsa_circ_0007494 down miR-616 PTEN inhibited cell proliferation, migration, and invasion 49 pairs of PCa tissues and adjacent normal tissues; C4-2, PC3, 22Rv1, DU145, LNCaP, and RWPE-1 cell lines Zhang et al.…”

“…95 In addition, Lin et al proposed that circDDX17 could inhibit proliferation, invasion, and EMT of PCa through the circDDX17/miR-346/LHPP signaling pathway. 99 Similarly, circAMOTL1L can upregulate the expression of E-cadherin by targeting the miR-193A-5P/PCDHA8 axis to prevent the metastasis of PCa. 65 In fact, the inhibition of EMT in PCa cells by p53 is also achieved through the circAMOTL1L/miR-193a-5P/PCDHA8 signaling pathway.…”

The Role of circRNAs in Human Papillomavirus (HPV)-Associated Cancers

“…circRNAs, with their multiple functions, are involved in many biological and pathological processes; they influence the progression of diseases, including viral infections and cancer [ 69 ]. In cancer, circRNAs influence the malignant phenotype by regulating specific cancer-related pathways and exert both an anti-cancer and pro-cancer action by acting as a tumor suppressor or oncogene [ 70 , 71 ]. They can be used as therapeutic targets in treatment.…”