期刊
CLINICAL AND TRANSLATIONAL MEDICINE
卷 11, 期 3, 页码 -出版社
JOHN WILEY & SONS LTD
DOI: 10.1002/ctm2.360
关键词
amoeboid migration; circRNA; circSOBP; metastasis; prostate cancer
资金
- National Science Foundation of Shanghai [18ZR1405800]
- Project for Key Medical Specialty Construction in Jinshan District (6th Period, Type A) [JSZK2019A03]
This study investigates the role of circSOBP in prostate cancer metastasis and finds that circSOBP suppresses PCa cell migration and invasion by sponging miR-141-3p and regulating the MYPT1/p-MLC2 axis. Overexpression of circSOBP inhibits metastasis, while depletion increases migration and induces amoeboid migration. The results suggest that circSOBP could be a potential therapeutic target for preventing prostate cancer metastasis.
Background Metastatic prostate cancer is a fatal disease despite multiple new approvals in recent years. Recent studies revealed that circular RNAs (circRNAs) can be involved in cancer metastasis. Defining the role of circRNAs in prostate cancer metastasis and discovering therapeutic targets that block cancer metastasis is of great significance for the treatment of prostate cancer. Methods The circSOBP levels in prostate cancer (PCa) were determined by qRT-PCR. We evaluated the function of circSOBP using a transwell assay and nude mice lung metastasis models. Immunofluorescence assay and electron microscopic assay were applied to determine the phenotypes of prostate cancer cells' migration. We used fluorescence in situ hybridization assay to determine the localization of RNAs. Dual luciferase and rescue assays were applied to verify the interactions between circSOBP, miR-141-3p, MYPT1, and phosphomyosin light chain (p-MLC2). Results We observed that circSOBP level was significantly lower in PCa specimens compared with adjacent noncancerous prostate specimens, and was correlated with the grade group of PCa. Overexpression of circSOBP suppressed PCa migration and invasion in vitro and metastasis in vivo. CircSOBP depletion increased migration and invasion and induced amoeboid migration of PCa cells. Mechanistically, circSOBP bound miR-141-3p and regulated the MYPT1/p-MLC2 axis. Moreover, the depletion of MYPT1 reversed the inhibitory effect of circSOBP on the migration and invasion of PCa cells. Complementary intronic Alu elements induced but were not necessary for the formation of circSOBP. The nuclear export of circSOBP was mediated by URH49. Conclusion Our results suggest that circSOBP suppresses amoeboid migration of PCa cells and inhibits migration and invasion through sponging miR-141-3p and regulating the MYPT1/p-MLC2 axis.
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