GPAA1 promotes the proliferation, invasion and migration of hepatocellular carcinoma cells by binding to RNA‑binding protein SF3B4

Ge,Song; Zhang,Qiang; Yang,Xiaoyong

doi:10.3892/ol.2022.13280

GPAA1 promotes the proliferation, invasion and migration of hepatocellular carcinoma cells by binding to RNA‑binding protein SF3B4

Authors:
- Song Ge
- Qiang Zhang
- Xiaoyong Yang
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Affiliations: Department of General Surgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221002, P.R. China
Published online on: March 22, 2022 https://doi.org/10.3892/ol.2022.13280
Article Number: 160
Copyright: © Ge et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

It has previously been reported that glycosylphosphatidylinositol anchor attachment 1 (GPAA1) is overexpressed in hepatocellular carcinoma (HCC); however, its role in regulating the development of HCC remains unknown. The present study aimed to examine the potential role of GPAA1 in HCC and to characterize the associated mechanism. The expression of GPAA1 was first examined using the Gene Expression Profiling Interactive Analysis 2 database, and was then determined using reverse transcription‑quantitative PCR and western blotting. The effects of GPAA1 silencing on the proliferation, colony formation, migration and invasion of HuH‑7 cells were measured using Cell Counting Kit‑8, colony formation, wound healing and Transwell assays, respectively. The interaction between splicing factor (SF)3B4 and GPAA1 was predicted by starBase and confirmed using RNA immunoprecipitation. The results of the present study demonstrated that GPAA1 was upregulated in HCC cells, and silencing GPAA1 markedly inhibited the proliferation, migration and invasion of HCC cells, which was accompanied by reduced levels of MMP2 and MMP9. In addition, it was observed that SF3B4 could bind to GPAA1. Furthermore, to confirm whether SF3B4 binds to GPAA1 to modulate HCC cell behavior, GPAA1 was knocked down and SF3B4 was overexpressed. Overexpression of SF3B4 reversed the effects of GPAA1 knockdown on the proliferation, migration and invasion of HCC cells. In conclusion, SF3B4 may promote the proliferation, invasion and migration of HCC cells by binding to GPAA1. The present study provided novel insight into the pathogenesis of HCC.

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1	Jemal A, Bray F, Center MM, Ferlay J, Ward E and Forman D: Global cancer statistics. CA Cancer J Clin. 61:69–90. 2011. View Article : Google Scholar : PubMed/NCBI
2	Schultheiß M, Bengsch B and Thimme R: Hepatocellular carcinoma. Dtsch Med Wochenschr. 146:1411–1420. 2021.(In German). PubMed/NCBI
3	Bruix J, Sherman M, Llovet JM, Beaugrand M, Lencioni R, Burroughs AK, Christensen E, Pagliaro L, Colombo M and Rodés J; EASL Panel of Experts on HCC, : Clinical management of hepatocellular carcinoma. Conclusions of the Barcelona-2000 EASL conference. European association for the study of the liver. J Hepatol. 35:421–430. 2001. View Article : Google Scholar : PubMed/NCBI
4	Llovet JM, Bru C and Bruix J: Prognosis of hepatocellular carcinoma: The BCLC staging classification. Semin Liver Dis. 19:329–338. 1999. View Article : Google Scholar : PubMed/NCBI
5	Zhang XX, Ni B, Li Q, Hu LP, Jiang SH, Li RK, Tian GA, Zhu LL, Li J, Zhang XL, et al: GPAA1 promotes gastric cancer progression via upregulation of GPI-anchored protein and enhancement of ERBB signalling pathway. J Exp Clin Cancer Res. 38:2142019. View Article : Google Scholar : PubMed/NCBI
6	Zhang JX, Wang JH, Sun XG and Hou TZ: GPAA1 promotes progression of childhood acute lymphoblastic leukemia through regulating c-myc. Eur Rev Med Pharmacol Sci. 24:4931–4939. 2020.PubMed/NCBI
7	Wu G, Guo Z, Chatterjee A, Huang X, Rubin E, Wu F, Mambo E, Chang X, Osada M, Sook Kim M, et al: Overexpression of glycosylphosphatidylinositol (GPI) transamidase subunits phosphatidylinositol glycan class T and/or GPI anchor attachment 1 induces tumorigenesis and contributes to invasion in human breast cancer. Cancer Res. 66:9829–9836. 2006. View Article : Google Scholar : PubMed/NCBI
8	Ho JC, Cheung ST, Patil M, Chen X and Fan ST: Increased expression of glycosyl-phosphatidylinositol anchor attachment protein 1 (GPAA1) is associated with gene amplification in hepatocellular carcinoma. Int J Cancer. 119:1330–1337. 2006. View Article : Google Scholar : PubMed/NCBI
9	Baralle FE and Giudice J: Alternative splicing as a regulator of development and tissue identity. Nat Rev Mol Cell Biol. 18:437–451. 2017. View Article : Google Scholar : PubMed/NCBI
10	Wang GS and Cooper TA: Splicing in disease: Disruption of the splicing code and the decoding machinery. Nat Rev Genet. 8:749–761. 2007. View Article : Google Scholar : PubMed/NCBI
11	Grosso AR, Martins S and Carmo-Fonseca M: The emerging role of splicing factors in cancer. EMBO Rep. 9:1087–1093. 2008. View Article : Google Scholar : PubMed/NCBI
12	Kim E, Goren A and Ast G: Insights into the connection between cancer and alternative splicing. Trends Genet. 24:7–10. 2008. View Article : Google Scholar : PubMed/NCBI
13	Shen Q and Nam SW: SF3B4 as an early-stage diagnostic marker and driver of hepatocellular carcinoma. BMB Rep. 51:57–58. 2018. View Article : Google Scholar : PubMed/NCBI
14	Iguchi T, Komatsu H, Masuda T, Nambara S, Kidogami S, Ogawa Y, Hu Q, Saito T, Hirata H, Sakimura S, et al: Increased copy number of the gene encoding SF3B4 indicates poor prognosis in hepatocellular carcinoma. Anticancer Res. 36:2139–2144. 2016.PubMed/NCBI
15	Shen Q, Eun JW, Lee K, Kim HS, Yang HD, Kim SY, Lee EK, Kim T, Kang K, Kim S, et al: Barrier to autointegration factor 1, procollagen-lysine, 2-oxoglutarate 5-dioxygenase 3, and splicing factor 3b subunit 4 as early-stage cancer decision markers and drivers of hepatocellular carcinoma. Hepatology. 67:1360–1377. 2018. View Article : Google Scholar : PubMed/NCBI
16	Kidogami S, Iguchi T, Sato K, Yoshikawa Y, Hu Q, Nambara S, Komatsu H, Ueda M, Kuroda Y, Masuda T, et al: SF3B4 plays an oncogenic role in esophageal squamous cell carcinoma. Anticancer Res. 40:2941–2946. 2020. View Article : Google Scholar : PubMed/NCBI
17	Zhou W, Ma N, Jiang H, Rong Y, Deng Y, Feng Y, Zhu H, Kuang T, Lou W, Xie D and Wang D: SF3B4 is decreased in pancreatic cancer and inhibits the growth and migration of cancer cells. Tumour Biol. 39:10104283176959132017. View Article : Google Scholar : PubMed/NCBI
18	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
19	Vainauskas S, Maeda Y, Kurniawan H, Kinoshita T and Menon AK: Structural requirements for the recruitment of Gaa1 into a functional glycosylphosphatidylinositol transamidase complex. J Biol Chem. 277:30535–30542. 2002. View Article : Google Scholar : PubMed/NCBI
20	Capurro M, Wanless IR, Sherman M, Deboer G, Shi W, Miyoshi E and Filmus J: Glypican-3: A novel serum and histochemical marker for hepatocellular carcinoma. Gastroenterology. 125:89–97. 2003. View Article : Google Scholar : PubMed/NCBI
21	Chen G, Li SY, Cai HY and Zuo FY: Enhanced expression and significance of glycosylphosphatidylinositol anchor attachment protein 1 in colorectal cancer. Genet Mol Res. 13:499–507. 2014. View Article : Google Scholar : PubMed/NCBI
22	Xing S, Li Z, Ma W, He X, Shen S, Wei H, Li ST, Shu Y, Sun L, Zhong X, et al: DIS3L2 promotes progression of hepatocellular carcinoma via hnRNP U-Mediated alternative splicing. Cancer Res. 79:4923–4936. 2019. View Article : Google Scholar : PubMed/NCBI
23	Oltean S and Bates DO: Hallmarks of alternative splicing in cancer. Oncogene. 33:5311–5318. 2014. View Article : Google Scholar : PubMed/NCBI
24	Lee SE, Alcedo KP, Kim HJ and Snider NT: Alternative splicing in hepatocellular carcinoma. Cell Mol Gastroenterol Hepatol. 10:699–712. 2020. View Article : Google Scholar : PubMed/NCBI
25	Xu W, Huang H, Yu L and Cao L: Meta-analysis of gene expression profiles indicates genes in spliceosome pathway are up-regulated in hepatocellular carcinoma (HCC). Med Oncol. 32:962015. View Article : Google Scholar : PubMed/NCBI