Molecular Cancer Multi-unit cooperation of Southern Medical University, Zhao Shanchao/Feng Ninghan/Chen Zhesheng discovered potential therapeutic targets for prostate cancer

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A growing body of research in iNature has shown that circular RNAs (circRNAs) play key regulatory roles in many cancers
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However, the underlying molecular mechanisms of circRNAs in prostate cancer (PCa) remain largely unknown
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On January 5, 2022, Zhao Shanchao from Southern Medical University, Feng Ninghan from Nanjing Medical University, and Chen Zhesheng from St.
John's University published a joint communication online in Molecular Cancer (IF=27) entitled "Hsa_circ_0003258 promotes prostate cancer metastasis by complexing with IGF2BP3 and sponging miR- 653-5p", which identified differentially expressed circRNAs by RNA sequencing
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Increased expression of hsa_circ_0003258 was found in PCa tissue and correlated with advanced TNM stage and ISUP grade
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Overexpression of hsa_circ_0003258 promoted PCa cell migration by inducing epithelial-mesenchymal transition (EMT) in vitro and tumor metastasis in vivo, whereas knockdown of hsa_circ_0003258 had the opposite effect
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Mechanistically, hsa_circ_0003258 could increase the expression of Rho GTPase activating protein 5 (ARHGAP5) by sponge miR-653-5p
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In addition, hsa_circ_0003258 physically bound to insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) in the cytoplasm, enhancing HDAC4 mRNA stability, activating the ERK signaling pathway, triggering EMT programming, and ultimately accelerating PCa metastasis
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In conclusion, this study found that upregulation of hsa_circ_0003258 drives tumor progression through the hsa_circ_0003258/miR-653-5p/ARHGAP5 axis and the hsa_circ_0003258/IGF2BP3/HDAC4 axis
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Hsa_circ_0003258 may serve as a promising biomarker for PCa metastasis and an attractive target for PCa intervention
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Prostate cancer (PCa) is a common cancer in men and the leading cause of cancer-related death in Western countries
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Localized prostate cancer can be cured with radical prostatectomy
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However, once the tumor has moved out of the gland, incurable metastatic disease is inevitable
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Metastasis of PCa is the main cause of death in patients, which greatly reduces the lifespan and quality of life of patients
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For patients with advanced metastatic PCa, current treatment options are limited and ineffective
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Therefore, identifying new biomarkers and therapeutic targets for metastatic PCa is a clinical imperative
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Circular RNAs (circRNAs) are single-stranded, covalently closed RNA molecules formed by back-splicing of pre-mRNAs and were originally thought to be byproducts of splicing errors
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However, many studies have shown that circRNAs are important regulators of gene expression and participate in multiple biological processes of tumorigenesis by acting as microRNA (miRNA) sponges, RNA-binding protein (RBP)-binding molecules, transcriptional regulators, or protein translation templates
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Schematic diagram of the article (picture from Molecular Cancer) It has been reported that circRNAs have multiple functions in regulating cell development, differentiation and metabolism
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In particular, studies have shown that abnormal expression of circRNAs is related to the invasion, migration and metastasis of cancer cells in distant organs
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For example, circCSNK1G3 promotes PCa cell growth by interacting with miR-181
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CircNOLC1 promotes PCa progression by sponging miR-647
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CircRHOBTB3 inhibits gastric cancer growth through miR-654-3p
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CircACTN4 promotes breast cancer progression by complexing with FUBP1
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CircSPARC promotes colorectal cancer progression by recruiting FUS
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These large numbers of reports suggest that circRNAs may serve as ideal biological targets for diagnosis and therapy, including PCa
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However, multiple circRNAs and their specific biological roles in PCa metastasis are worth exploring
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In this study, a circRNA from ZNF652 exons 4 and 5 (circBase ID: hsa_circ_0003258) was identified as a novel oncogene in PCa
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This study found that hsa_circ_0003258 was significantly upregulated in PCa tissues and was associated with the metastasis of PCa cells
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Mechanistically, hsa_circ_0003258 directly interacts with the RNA-binding protein IGF2BP3 to enhance the stability of histone deacetylase 4 (HDAC4) mRNA, resulting in PCa invasiveness
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Furthermore, hsa_circ_0003258 may upregulate the expression of Rho GTPase-activating protein 5 (ARHGAP5) to promote tumor progression by sponging miR-653-5p
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This work demonstrates the important role of hsa_circ_0003258 in PCa progression
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Reference message: https://molecular-cancer.
biomedcentral.
com/articles/10.
1186/s12943-021-01480-x