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Lab Invest. 2019 Feb;99(2):191-199. doi: 10.1038/s41374-018-0138-0. Epub 2018 Oct 5.

Mitochondrial pyruvate carrier 1 functions as a tumor suppressor and predicts the prognosis of human renal cell carcinoma.

Author information

1
Department of Nephrology, Southwest Hospital, Third Military Medical University (Army Medical University), 400038, Chongqing, China.
2
Institute of Pathology, Southwest Hospital, Third Military Medical University (Army Medical University), 400038, Chongqing, China.
3
Institute of Pathology, Southwest Hospital, Third Military Medical University (Army Medical University), 400038, Chongqing, China. bianxiuwu@263.net.
4
Department of Nephrology, Southwest Hospital, Third Military Medical University (Army Medical University), 400038, Chongqing, China. wuxiongfei18@hotmail.com.

Abstract

Invasion and subsequent metastasis are major characteristics of malignant human renal cell carcinoma (RCC), though the mechanisms remain elusive. Mitochondrial pyruvate carrier (MPC), a key factor that controls pyruvate transportation in mitochondria, is frequently dysregulated in tumor cells and loss of MPC predicts poor prognosis in various types of cancer. However, the clinical relevance and functional significance of MPC in RCC remain to be elucidated. In this study, we investigated the expression of MPC1 and MPC2 in specimens from RCC patients and observed downregulation of MPC1, but not MPC2, in RCC tissues compared with adjacent non-cancerous tissue. Moreover, RCC patients with higher MPC1 expression exhibited longer overall survival rate than those with lower MPC1. Functionally, MPC1 suppressed the invasion of RCC cells in vitro and reduced the growth of RCC cells in vivo, possibly through inhibition of MMP7 and MMP9. Further studies revealed that loss of MPC1 was induced by hypoxia in RCC cells, and notably, MPC1 expression, was negatively correlated with HIF1α expression in RCC cells and patient samples. Taken together, our results identify anti-tumor function of MPC1 in RCC and revealed MPC1 as a novel prognostic biomarker to predict better patient survival.

PMID:
30291323
DOI:
10.1038/s41374-018-0138-0

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