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Upregulated calcium‐binding tyrosine phosphorylation‐regulated protein‐a/b regulates cell proliferation and apoptosis and predicts poor prognosis in hepatocellular carcinoma
Author(s) -
Yu XiangNan,
Guo HongYing,
Liu TaoTao,
Zhang GuangCong,
Zhu HaiRong,
Shi Xuan,
Song GuangQi,
Jiang XueMei,
Huang XiaoXi,
Weng ShuQiang,
Dong Ling,
Shen XiZhong,
Huang YangQing,
Zhu JiMin
Publication year - 2020
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.29538
Subject(s) - downregulation and upregulation , hepatocellular carcinoma , cancer research , cyclin d1 , apoptosis , tyrosine phosphorylation , cell growth , biology , cell cycle , microbiology and biotechnology , kinase , biochemistry , gene
Background Calcium‐binding tyrosine phosphorylation‐regulated protein (CABYR) is a group of isoforms produced by alternative splicing and is overexpressed in human malignancies including hepatocellular carcinoma (HCC). However, the prognostic value and biological functions of its major protein isoforms, named CABYR‐a/b (combined CABYR‐a and CABYR‐b), in HCC remain to be established. Methods CABYR‐a/b expression was detected in HCC tissues and cell lines by quantitative real‐time polymerase chain reaction and Western blot analysis. The correlation of CABYR‐a/b expression with clinical characteristics and its prognosis impact were determined by statistical analysis. Finally, the biological functions and molecular mechanism of CABYR‐a/b were also investigated using molecular biology approaches. Results The present research found that CABYR‐a/b was markedly elevated in HCC specimens and cell lines. Upregulated CABYR‐a/b level had positive association with tumor size and differentiation in patients. Moreover, cases with elevated CABYR‐a/b level had poorer overall survival (OS) and disease‐free survival (DFS) than those with reduced CABYR‐a/b level. Multivariate analysis and prognostic nomograms demonstrated that CABYR‐a/b overexpression was an independent predictive indicator for OS and DFS. The calibration curve for the odds of OS and DFS demonstrated that the prediction by nomograms was in excellent accordance with actual situation. CABYR‐a/b downregulation suppressed cell proliferation and induced G1‐phase arrest via decreasing cyclin D1 and cyclin dependent kinase 4, while promoted apoptosis by reducing B‐cell lymphoma 2 (Bcl‐2) and increasing Bcl‐2‐associated death promoter. Conclusion Our research indicates that CABYR‐a/b exerts an oncogenic effect on HCC development and may become a new prognostic indicator for patients with HCC.