Cancer Management and Research (Mar 2020)

Expression of Carboxypeptidase X M14 Family Member 2 Accelerates the Progression of Hepatocellular Carcinoma via Regulation of the gp130/JAK2/Stat1 Pathway

  • Ye Y,
  • An Y,
  • Wang M,
  • Liu H,
  • Guan L,
  • Wang Z,
  • Li W

Journal volume & issue
Vol. Volume 12
pp. 2353 – 2364

Abstract

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Yanshuo Ye,1 Yuan An,1 Min Wang,2 Hongyu Liu,1 Lianyue Guan,1 Zhanpeng Wang,1 Wei Li1 1Department of Hepatobiliary-Pancreatic Surgery, China-Japan Union Hospital of Jilin University, Changchun, People’s Republic of China; 2Department of Pathology, Jilin Provincial Cancer Hospital, Changchun 130012, People’s Republic of ChinaCorrespondence: Wei LiDepartment of Hepatobiliary-Pancreatic Surgery, China-Japan Union Hospital of Jilin University, Changchun, People’s Republic of ChinaEmail [email protected]: Carboxypeptidase X, M14 family member 2 (CPXM2) has been reported to be involved with several human malignancies. However, the impact of CPXM2 on human hepatocellular carcinoma (HCC) tumorigenesis has not been studied.Materials and Methods: Using immunohistochemistry, the detailed CPXM2 expression patterns were examined in HCC cell lines and tissues. Additionally, a hepatic stellate cell line overexpressing CPXM2 and an HCC CPXM2-knockdown cell line were established by lipofection of an expression plasmid or short hairpin RNA, respectively. The transfection efficiencies were confirmed by reverse transcription-quantitative PCR, Western blotting and immunofluorescence. Moreover, Western blotting was conducted to determine the phosphorylation levels of the tyrosine kinase 2 (JAK2)/signal transducer and activator of transcription 3 (Stat1) pathway. Furthermore, gp130-specific hairpin RNA was used to knockdown gp130 expression in hepatic stellate cells overexpressing CPXM2. The malignant phenotype of cultured HCC cells was assessed by a Cell Counting Kit-8 (CCK8) assay, plate cloning assay, Matrigel invasion assay and wound-healing assay in vitro.Results: It was demonstrated that CPXM2 was upregulated in HCC, and its upregulation predicted a poor prognosis. Besides, the upregulation of CPXM2 markedly enhanced the metastatic potential of HCC via the gp130/JAK2/Stat1 signaling pathway in vitro.Conclusion: In summary, this evidence suggests a positive role for CPXM2 in HCC progression via modulation of the gp130/JAK2/Stat1 signaling pathway in HCC.Keywords: carboxypeptidase XM14 family member 2, hepatocellular carcinoma, metastasis

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