A Coiled-Coil Domain Containing 50 Splice Variant Is Modulated by Serine/Arginine-Rich Splicing Factor 3 and Promotes Hepatocellular Carcinoma in Mice by the Ras Signaling Pathway

Hepatology : Official Journal of the American Association for the Study of Liver Diseases
Hong WangJing-Ping Yun

Abstract

Deregulation of alternative splicing contributes to the malignant progression of cancer. Little is known about the significant alternative splicing events in hepatocellular carcinoma (HCC). High-throughput sequencing revealed that coiled-coil domain containing 50 (CCDC50) pre-mRNA is aberrantly spliced in 50% of our HCC cases. A BaseScope assay was performed to examine the expression of CCDC50S (a truncated oncogenic splice variant) in HCC tissues. Compared with benign liver tumors and several other types of solid tumors, CCDC50S mRNA was up-regulated in HCC, with a diagnostic potential (sensitivity, 0.711; specificity, 0.793). High expression of CCDC50S mRNA in HCC was significantly correlated with poor tumor differentiation, advanced tumor node metastasis (TNM) stage, and unfavorable prognosis. Overexpression of CCDC50S exerted tumorigenic activities that promoted HCC growth and metastasis by activation of Ras/forkhead box protein O4 (Foxo4) signaling. Either suppression of mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) phosphorylation or overexpression of Foxo4 markedly attenuated CCDC50S-mediated phenotypes. Furthermore, serine- and arginine-rich splicing factor 3 (SRSF3) directly ...Continue Reading

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Citations

Jan 14, 2020·Cell Biology International·Ningfu PengShaoliang Zhu
Jul 29, 2020·Cancer Immunology, Immunotherapy : CII·Chunxia ZhangWeipeng Wang
Jun 21, 2020·Journal of Experimental & Clinical Cancer Research : CR·Guoliang SunHua Xu
Jan 26, 2021·BioMed Research International·Zhan-Dong HuJun Yan
Feb 26, 2021·Molecular Carcinogenesis·Jianyi WangTianzhen Wang
Mar 16, 2021·Frontiers in Endocrinology·Panyisha WuNicholas J G Webster

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