SCUBE3 downregulation modulates hepatocellular carcinoma by inhibiting CCNE1 via TGFβ/PI3K/AKT/GSK3β pathway
Abstract Objectives We aimed to verify the role of signal peptide-CUB-EGF-like domain-containing protein3 (SCUBE3) in the hepatocellular carcinoma (HCC) progression. Methods The role of SCUBE3 in HCC cell proliferation, apoptosis, and cell cycle in vitro were detected using MTT assay, colony formati...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-01-01
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| Series: | Cancer Cell International |
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| Online Access: | https://doi.org/10.1186/s12935-021-02402-z |
| _version_ | 1798034666388717568 |
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| author | Pan Xu Aoran Luo Chuan Xiong Hong Ren Liang Yan Qiang Luo |
| author_facet | Pan Xu Aoran Luo Chuan Xiong Hong Ren Liang Yan Qiang Luo |
| author_sort | Pan Xu |
| collection | DOAJ |
| description | Abstract Objectives We aimed to verify the role of signal peptide-CUB-EGF-like domain-containing protein3 (SCUBE3) in the hepatocellular carcinoma (HCC) progression. Methods The role of SCUBE3 in HCC cell proliferation, apoptosis, and cell cycle in vitro were detected using MTT assay, colony formation assay, 5-ethynyl-2´-deoxyuridine assay (EDU), Celigo cell counting assay, Caspase3/7 activity assay, and flow cytometry. The effect of SCUBE3 on HCC cell proliferation in vivo was inspected by a xenograft tumour model in nude mice. The related mechanisms were further studied. Results The level of SCUBE3 was upregulated in HCC tissues and cell lines. Knockdown of SCUBE3 inhibited proliferation, promoted apoptosis, and induced cell cycle arrest in HCC cell lines in vitro and in vivo. Screening of cell cycle-related proteins revealed that CCNL2, CDK6, CCNE1, and CCND1 exhibited a significantly different expression profile. We found that SCUBE3 may promote the proliferation of HCC cells by regulating CCNE1 expression. The pathway enrichment analysis showed that the TGFβ signalling pathway and the PI3K/AKT signalling pathway were significantly altered. Co-immunoprecipitation results showed that SCUBE3 binds to the TGFβRII receptor. SCUBE3 knockdown inhibited the PI3K/AKT signalling pathway and the phosphorylation of GSK3β to inhibit its kinase activity. Conclusions SCUBE3 promotes HCC development by regulating CCNE1 via TGFβ/PI3K/AKT/GSK3β pathway. In addition, SCUBE3 may be a new molecular target for the clinical diagnosis and treatment of HCC. |
| first_indexed | 2024-04-11T20:47:27Z |
| format | Article |
| id | doaj.art-b385aaa6905f4f91a78fcc1408c3e0d5 |
| institution | Directory Open Access Journal |
| issn | 1475-2867 |
| language | English |
| last_indexed | 2024-04-11T20:47:27Z |
| publishDate | 2022-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer Cell International |
| spelling | doaj.art-b385aaa6905f4f91a78fcc1408c3e0d52022-12-22T04:03:58ZengBMCCancer Cell International1475-28672022-01-0122111910.1186/s12935-021-02402-zSCUBE3 downregulation modulates hepatocellular carcinoma by inhibiting CCNE1 via TGFβ/PI3K/AKT/GSK3β pathwayPan Xu0Aoran Luo1Chuan Xiong2Hong Ren3Liang Yan4Qiang Luo5Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical UniversityKey Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical UniversityBiotechnology and Nuclear Technology Research Institute, Sichuan Academy of Agricultural SciencesKey Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical UniversityClinical Laboratory Department, Chongqing Hygeia Cancer HospitalKey Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical UniversityAbstract Objectives We aimed to verify the role of signal peptide-CUB-EGF-like domain-containing protein3 (SCUBE3) in the hepatocellular carcinoma (HCC) progression. Methods The role of SCUBE3 in HCC cell proliferation, apoptosis, and cell cycle in vitro were detected using MTT assay, colony formation assay, 5-ethynyl-2´-deoxyuridine assay (EDU), Celigo cell counting assay, Caspase3/7 activity assay, and flow cytometry. The effect of SCUBE3 on HCC cell proliferation in vivo was inspected by a xenograft tumour model in nude mice. The related mechanisms were further studied. Results The level of SCUBE3 was upregulated in HCC tissues and cell lines. Knockdown of SCUBE3 inhibited proliferation, promoted apoptosis, and induced cell cycle arrest in HCC cell lines in vitro and in vivo. Screening of cell cycle-related proteins revealed that CCNL2, CDK6, CCNE1, and CCND1 exhibited a significantly different expression profile. We found that SCUBE3 may promote the proliferation of HCC cells by regulating CCNE1 expression. The pathway enrichment analysis showed that the TGFβ signalling pathway and the PI3K/AKT signalling pathway were significantly altered. Co-immunoprecipitation results showed that SCUBE3 binds to the TGFβRII receptor. SCUBE3 knockdown inhibited the PI3K/AKT signalling pathway and the phosphorylation of GSK3β to inhibit its kinase activity. Conclusions SCUBE3 promotes HCC development by regulating CCNE1 via TGFβ/PI3K/AKT/GSK3β pathway. In addition, SCUBE3 may be a new molecular target for the clinical diagnosis and treatment of HCC.https://doi.org/10.1186/s12935-021-02402-zHepatocellular carcinomaSCUBE3AKTCCNE1Cell proliferation |
| spellingShingle | Pan Xu Aoran Luo Chuan Xiong Hong Ren Liang Yan Qiang Luo SCUBE3 downregulation modulates hepatocellular carcinoma by inhibiting CCNE1 via TGFβ/PI3K/AKT/GSK3β pathway Cancer Cell International Hepatocellular carcinoma SCUBE3 AKT CCNE1 Cell proliferation |
| title | SCUBE3 downregulation modulates hepatocellular carcinoma by inhibiting CCNE1 via TGFβ/PI3K/AKT/GSK3β pathway |
| title_full | SCUBE3 downregulation modulates hepatocellular carcinoma by inhibiting CCNE1 via TGFβ/PI3K/AKT/GSK3β pathway |
| title_fullStr | SCUBE3 downregulation modulates hepatocellular carcinoma by inhibiting CCNE1 via TGFβ/PI3K/AKT/GSK3β pathway |
| title_full_unstemmed | SCUBE3 downregulation modulates hepatocellular carcinoma by inhibiting CCNE1 via TGFβ/PI3K/AKT/GSK3β pathway |
| title_short | SCUBE3 downregulation modulates hepatocellular carcinoma by inhibiting CCNE1 via TGFβ/PI3K/AKT/GSK3β pathway |
| title_sort | scube3 downregulation modulates hepatocellular carcinoma by inhibiting ccne1 via tgfβ pi3k akt gsk3β pathway |
| topic | Hepatocellular carcinoma SCUBE3 AKT CCNE1 Cell proliferation |
| url | https://doi.org/10.1186/s12935-021-02402-z |
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