Hsa_circ_0030586 promotes epithelial–mesenchymal transition in prostate cancer via PI3K-AKT signaling

Abstract

Circular RNAs (CircRNAs) gain importance as regulatory molecules in prostate cancer (PCa), but molecular mechanism of most circRNAs in pathogenesis of PCa remains to be studied. This study aimed to explore the role of hsa_circ_0030586 in PCa. Gene Expression Omnibus database (GSE77661) was used to screen out candidate circRNAs. Quantitative real-time PCR was used to verify the relative expressions of circRNAs, miRNAs, and genes in PCa cells. A CCK-8 assay was used to evaluate the cells’ proliferation. Transwell and wound healing assay were used to determine the cells’ migration and invasion. Western blotting and immunohistochemistry were used to detect the protein expression of PI3K/AKT signaling proteins and epithelial–mesenchymal transition (EMT) markers. Furthermore, a nude mice tumorigenesis experiment in vivo was conducted to determine the function of hsa_circ_0030586 on PCa. Our results showed that hsa_circ_0030586 is significantly upregulated in PCa cells (p < 0.05). Its circular structure was confirmed via agarose gel electrophoresis and Sanger sequencing. Interfering with hsa_circ_0030586 in PC3 cells inhibited cell proliferation, migration, and invasion and led to the significant upregulation of E-cadherin and the significant downregulation of p-AKT/AKT, IKKα, PIK3CB, and Twist (all p < 0.05). Conversely, the hsa_circ_003058 interference fragment combined with the transfection of a miR-145-3p inhibitor could reverse the above effects. In vivo tumorigenesis of the xenograft model confirmed that interfering with hsa_circ_0030586 suppressed tumor cell proliferation and inhibited PI3K-AKT signaling and EMT in PC3 cells. Hsa_circ_0030586 is significantly upregulated in PCa cells and may promote EMT via PI3K-AKT signaling.

The function and mechanisms of action of circular RNAs in Urologic Cancer

“…Circ0016068 sequesters miR-330-3p and releases BMI-1 to enhance PCa cell proliferation, migration, and invasion, as well as xenograft tumor metastasis. Circ0030586 was found to be highly expressed in PCa cells using the GEO database [ 170 ]. Knockdown of circ0030586 in PC3 cells inhibited PCa cell proliferation, migration and invasion, and resulted in significant up-regulation of E-cadherin and significant down-regulation of p-AKT/AKT, IKKα, PIK3CB, and Twist.…”

Identification of a dysregulated CircRNA-associated gene signature for predicting prognosis, immune landscape, and drug candidates in bladder cancer

“…Of note, our previous studies (16,17) confirmed that the circ_0026782, circ_0004826, circ_0077837, circ_0001946, and circ_0030586 were significantly downregulated, whereas circ_0003141 and circ_0008039 was dramatically upregulated in BCa vs. paired non-tumorous tissues, which were consistent with our circRNA sequencing data; besides, circ_0077837, circ_0004826 and circ_0030586 served as tumor suppressors and prognosis predictors in BCa. Additionally, some circRNA among our sequencing such as circ_0008039, circ_0000745, circ_000074, circ_0077837, circ_0030586, and circ_0001946, etc, were also closely associated with malignant biological behavior of other cancer types (37)(38)(39)(40)(41)(42).…”

circSPECC1 Promotes Proliferation and Migration of LNCaP Prostate Cancer Cells by Affecting Their Epithelial-Mesenchymal Transition

“…Thus, circSPECC1 promoted the proliferation and migration of LNCaP prostate cancer cells by affecting EMT. Similarly, hsa_circ_0030586 is significantly overexpressed in prostate cancer cells, and downregulation of hsa_circ_0030586 can reduce the proliferative, migratory, and invasive ability of prostate cancer cells and further inhibit their EMT [ 18 ]. In addition, hsa_circ_0001085 may indirectly regulate the PI3K-Akt and TGF- β signaling pathways through hsa_miR-196b-5P and the MAPK signaling pathway through hsa_miR-451A, thereby playing a regulatory role in the EMT-induced model of prostate cancer cells [ 19 ].…”