SNRPB Modulates Hepatocellular Carcinoma Malignancy via the Hippo Signaling Pathway

HU Xinyue; LOU Lei; DAI Qianlong; PENG Shuchang; GUO Xiaowei

PDF(7035 KB)

Journal of Hunan Normal University(Medical Science) ›› 2025, Vol. 22 ›› Issue (6) : 1-7.

Basic Medicine

SNRPB Modulates Hepatocellular Carcinoma Malignancy via the Hippo Signaling Pathway

HU Xinyue, LOU Lei, DAI Qianlong, PENG Shuchang, GUO Xiaowei

Author information +

History +

Abstract

Objective To investigate the oncogenic role of small nuclear ribonucleoprotein polypeptides B and B1 (SNRPB) in hepatocellular carcinoma (HCC) and its underlying molecular mechanisms. Methods Multi-omics databases were utilized to analyze the expression and clinical significance of SNRPB in HCC. The effects of SNRPB on HCC cell migration and invasion were evaluated using Western blot and Transwell assay. The molecular mechanisms of SNRPB in regulating the Hippo signaling pathway were investigated through dual-luciferase reporter assay, co-immunoprecipitation (Co-IP), and ubiquitination assays. Results SNRPB was highly expressed in HCC tissues and cell lines, and its expression was significantly associated with poor prognosis in patients. Functional experiments demonstrated that SNRPB promoted HCC cell migration and invasion. Mechanistic studies revealed that SNRPB interacted with YAP protein, inhibited its ubiquitination-mediated degradation, and thereby stabilized YAP protein, enhancing the transcriptional activity of the downstream target gene CTGF. Furthermore, YAP positively regulated SNRPB expression, forming a SNRPB-YAP positive feedback loop. Conclusion SNRPB promotes HCC progression by modulating the Hippo signaling pathway, offering a novel potential therapeutic target for HCC treatment.

Key words

SNRPB / RNA-binding proteins / Hippo signaling pathway / hepatocellular carcinoma

Cite this article

EndNote

Ris (Procite)

Bibtex

Download Citations

HU Xinyue, LOU Lei, DAI Qianlong, PENG Shuchang, GUO Xiaowei. SNRPB Modulates Hepatocellular Carcinoma Malignancy via the Hippo Signaling Pathway[J]. Journal of Hunan Normal University(Medical Science). 2025, 22(6): 1-7

References

[1] SUNG H, FERLAY J, SIEGEL R L, et al.Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries[J]. CA Cancer J Clin, 2021, 71(3): 209-249.
[2] IN DER STROTH L, THAREHALLI U, GÜNES C, et al. Telomeres and Telomerase in the Development of Liver Cancer[J]. Cancers (Basel), 2020, 12(8): 2048.
[3] WANG Y, DENG B.Hepatocellular carcinoma: molecular mechanism, targeted therapy, and biomarkers[J]. Cancer Metastasis Rev, 2023, 42(3): 629-652.
[4] FINN R S, QIN S, IKEDA M, et al.Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma[J]. N Engl J Med, 2020, 382(20): 1894-1905.
[5] LIU D, LI Q, ZANG Y, et al.USP1 modulates hepatocellular carcinoma progression via the Hippo/TAZ axis[J]. Cell Death Dis, 2023, 14(4): 264.
[6] PAN D.The Hippo Signaling Pathway in Development and Cancer[J]. Dev Cell, 2010, 19(4): 491-505.
[7] KWON Y, VINAYAGAM A, SUN X, et al.The Hippo signaling pathway interactome[J]. Science, 2013, 342(6159): 737-740.
[8] ZHANG P, PEI C, WANG X, et al. A Balance of Yki/Sd Activator and E2F1/Sd Repressor Complexes Controls Cell Survival and Affects Organ Size[J]. Dev Cell, 2017, 43(5): 603-617. e5.
[9] GUO Y, ZHU Z, HUANG Z, et al.CK2-induced cooperation of HHEX with the YAP-TEAD4 complex promotes colorectal tumorigenesis[J]. Nat Commun, 2022, 13(1): 4995.
[10] LIU T, ZHOU J, CHEN Y, et al.Genome-Wide Characterization of TAZ Binding Sites in Mammary Epithelial Cells[J]. Cancers (Basel), 2023, 15(19): 4713.
[11] ZHANG P, LIU D, ZANG Y, et al.USP12 facilitates gastric cancer progression via stabilizing YAP[J]. Cell Death Discov, 2024, 10(1): 174.
[12] FRANKLIN J M, WU Z, GUAN K-L.Insights into recent findings and clinical application of YAP and TAZ in cancer[J]. Nat Rev Cancer, 2023, 23(8): 512-525.
[13] PEREIRA B, BILLAUD M, ALMEIDA R.RNA-Binding Proteins in Cancer: Old Players and New Actors[J]. Trends Cancer, 2017, 3(7): 506-528.
[14] PENG S, LI C, HE Y, et al.Regulatory roles of RNA binding proteins in the Hippo pathway[J]. Cell Death Discov, 2025, 11(1): 36.
[15] GRAY T A, SMITHWICK M J, SCHALDACH M A, et al.Concerted regulation and molecular evolution of the duplicated SNRPB'/B and SNRPN loci[J]. Nucleic Acids Res, 1999, 27(23): 4577-4584.
[16] ZHAN Y T, LI L, ZENG T T, et al.SNRPB-mediated RNA splicing drives tumor cell proliferation and stemness in hepatocellular carcinoma[J]. Aging (Albany NY), 2020, 13(1): 537-554.
[17] LIU N, WU Z, CHEN A, et al.SNRPB promotes the tumorigenic potential of NSCLC in part by regulating RAB26[J]. Cell Death Dis, 2019, 10(9): 667.
[18] CORREA B R, DE ARAUJO P R, QIAO M, et al. Functional genomics analyses of RNA-binding proteins reveal the splicing regulator SNRPB as an oncogenic candidate in glioblastoma[J]. Genome Biol, 2016, 17(1): 125.
[19] GUO X, SUN Y, AZAD T, et al.Rox8 promotes microRNA-dependent yki messenger RNA decay[J]. Proc Natl Acad Sci U S A, 2020, 117(48): 30520-30530.
[20] GAO R, KALATHUR R K R, COTO-LLERENA M, et al. YAP/TAZ and ATF4 drive resistance to Sorafenib in hepatocellular carcinoma by preventing ferroptosis[J]. EMBO Mol Med, 2021, 13(12): e14351.
[21] LIU Y, ZHUO S, ZHOU Y, et al.Yap-Sox9 signaling determines hepatocyte plasticity and lineage-specific hepatocarcinogenesis[J]. J Hepatol, 2022, 76(3): 652-664.
[22] YU F X, ZHAO B, PANUPINTHU N, et al.Regulation of the Hippo-YAP pathway by G-protein-coupled receptor signaling[J]. Cell, 2012, 150(4): 780-791.
[23] WANG J, YU H, DONG W, et al.N6-Methyladenosine-Mediated Up-Regulation of FZD10 Regulates Liver Cancer Stem Cells' Properties and Lenvatinib Resistance Through WNT/β-Catenin and Hippo Signaling Pathways[J]. Gastroenterol, 2023, 164(6): 990-1005.
[24] GU Y, WANG Y, SHA Z, et al.Transmembrane protein KIRREL1 regulates Hippo signaling via a feedback loop and represents a therapeutic target in YAP/TAZ-active cancers[J]. Cell Rep, 2022, 40(9): 111296.