OncoTargets and Therapy (Jul 2020)

Methylcrotonoyl-CoA Carboxylase 2 Promotes Proliferation, Migration and Invasion and Inhibits Apoptosis of Prostate Cancer Cells Through Regulating GLUD1-P38 MAPK Signaling Pathway

  • He J,
  • Mao Y,
  • Huang W,
  • Li M,
  • Zhang H,
  • Qing Y,
  • Lu S,
  • Xiao H,
  • Li K

Journal volume & issue
Vol. Volume 13
pp. 7317 – 7327

Abstract

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Jianwen He,* Yunhua Mao,* Wentao Huang,* Mingzhao Li, Huimin Zhang, Yunhao Qing, Shuo Lu, Hengjun Xiao, Ke Li Department of Urology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ke Li Email [email protected] Xiao Email [email protected]: Prostate cancer (PCa) is the most common cancer in American men, and the mechanisms of development and progression are still not completely clear. Methylcrotonoyl-CoA carboxylase 2 (MCCC2) was previously identified overexpressed in PCa with lymph node metastasis, but its specific role and mechanisms need further investigation. This study aimed to investigate the role of MCCC2 in PCa cells and its underlying mechanisms.Materials and Methods: Quantitative RT-PCR and Western blotting were used to detect MCCC2 mRNA and protein expression in normal prostate epithelium and cancerous cells. Upon manipulation of MCCC2 expression, cell proliferation was measured by CCK-8 assays and migration and invasion were determined by transwell assays. Changes of apoptosis, cell cycle and mitochondrial membrane potential were evaluated by flow cytometry. MCCC2-mediated signaling pathways were screened by bioinformatics and verified by RT-PCR and Western blotting. Finally, immunohistochemistry was performed to detect the expression of MCCC2 and glutamate dehydrogenase 1 (GLUD1) in PCa tissues to analyze their correlation.Results: We demonstrated that MCCC2 promoted cell proliferation, migration and invasion but inhibited apoptosis in PCa cells. In addition, MCCC2 in 22Rv1 cells induced mitochondrial damage. In PCa tissues, MCCC2 overexpression associated with lymph node metastasis (P=0.001) and high Gleason scores (P< 0.001). MCCC2 positively correlated with GLUD1 expression in PCa tissues (r=0.435, P< 0.001). Ectopic overexpression of MCCC2 up-regulated GLUD1 and p38 MAPK expression, whereas inhibition of MCCC2 decreased GLUD1 and p38 MAPK expression.Conclusion: MCCC2 exerts oncogenic function in PCa through regulating GLUD1-p38 MAPK signaling pathway, and it may be a potential treatment target.Keywords: prostate cancer, MCCC2, GLUD1, p38 MAPK

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