BMB Rep. 2015; 48(11): 597-598  
Mitochondrial defect-responsive gene signature in liver-cancer progression
Young-Kyoung Lee1,3, Hyun Goo Woo2,3 & Gyesoon Yoon1,3,*
Departments of 1Biochemistry and 2Physiology, Ajou University School of Medicine, Suwon 16499, 3Department of Biomedical Science, Graduate School, Ajou University, Suwon 16499, Korea
Correspondence to: E-mail: ypeace@ajou.ac.kr
Received: August 27, 2015; Published online: November 30, 2015.
© Korean Society for Biochemistry and Molecular Biology. All rights reserved.

Abstract
Mitochondrial respiratory defect is a key bioenergetics feature of hepatocellular carcinoma (HCC) cells. However, their involvement and roles in HCC development and progression remain unclear. Recently, we identified 10 common mitochondrial defect (CMD) signature genes that may be induced by retrograde signaling-mediated transcriptional reprogramming in response to HCC mitochondrial defects. HCC patients with enriched expression of these genes had poor prognostic outcomes, such as shorter periods of overall survival and recurrence- free survival. Nuclear protein 1 (NUPR1), a key transcription regulator, was up-regulated by Ca++-mediated retrograde signaling. NUPR1-centric network analysis and a biochemical promoter-binding assay demonstrated that granulin (GRN) is a key downstream effector of NUPR1 for the regulation of HCC cell invasiveness; association analysis of the NUPR1-GRN pathway supported this conclusion. Mitochondrial respiratory defects and retrograde signaling thus play pivotal roles in HCC progression, highlighting the potential of the NUPR1-GRN axis as a novel diagnostic marker and therapeutic target for HCC.
Keywords: Gene signature, Hepatocellular carcinoma, Mitochondrial defect, Retrograde signal, Transcription regulator


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