PMID- 29158991
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220310
IS  - 2167-8359 (Print)
IS  - 2167-8359 (Electronic)
IS  - 2167-8359 (Linking)
VI  - 5
DP  - 2017
TI  - NDUFA4L2 is associated with clear cell renal cell carcinoma malignancy and is 
      regulated by ELK1.
PG  - e4065
LID - 10.7717/peerj.4065 [doi]
LID - e4065
AB  - BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is the most common and lethal 
      cancer of the adult kidney. However, its pathogenesis has not been fully 
      understood till now, which hinders the therapeutic development of ccRCC. NADH 
      dehydrogenase (ubiquinone) 1 alpha subcomplex 4-like 2 (NDUFA4L2) was found to be 
      upregulated and play an important role in ccRCC. We aimed to further investigate 
      the underlying mechanisms by which NDUFA4L2 exerted function and its expression 
      level was upregulated. METHODS: The Gene Expression Omnibus (GEO) and The Cancer 
      Genome Atlas (TCGA) data were mined to verify the change of NDUFA4L2 expression 
      level in ccRCC tissues. The correlation between expression level of NDUFA4L2 and 
      cell proliferation/apoptosis was explored by Gene Set Enrichment Analysis (GSEA). 
      Protein-protein interaction (PPI) network of NDUFA4L2 was constructed. Biological 
      process and involved pathways of NDUFA4L2 were analyzed by gene ontology (GO) and 
      the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. The transcription 
      factors (TFs) which can induce the expression of NDUFA4L2 were explored in 
      clinical samples by correlation analysis and its regulation on the expression of 
      NDUFA4L2 was verified by knockdown experiment. RESULTS: NDUFA4L2 was verified to 
      be overexpressed in ccRCC tissues and its expression level was increased 
      accordingly as the American Joint Committee on Cancer (AJCC) stage progressed. A 
      high NDUFA4L2 level predicted the poor prognosis of ccRCC patients and correlated 
      with enhanced cell proliferation and anti-apoptosis. NDUFA4L2 may interact with 
      14 tumor-related proteins, participate in growth and death processes and be 
      involved in ccRCC-related pathways, such as insulin-like growth factor 1 (IGF-1), 
      mammalian target of Rapamycin (mTOR) and phosphoinositide 3 kinase 
      serine/threonine protein kinase (PI3K/AKT). ETS domain-containing protein ELK1 
      level positively correlated with the level of NDUFA4L2 in ccRCC tissues and ELK1 
      could regulate the expression of NDUFA4L2 in ccRCC cells. DISCUSSION: NDUFA4L2 
      upregulation was associated with ccRCC malignancy. NDUFA4L2 expression was 
      regulated by ELK1 in ccRCC cells. Our study provided potential mechanisms by 
      which NDUFA4L2 affected ccRCC occurrence and progression.
FAU - Wang, Lei
AU  - Wang L
AD  - Department of Urology, Beijing Friendship Hospital, Capital Medical University, 
      Beijing, China.
FAU - Peng, Zhiqiang
AU  - Peng Z
AD  - Department of Biochemistry and Molecular Biology, Capital Medical University, 
      Beijing, China.
FAU - Wang, Kaizhen
AU  - Wang K
AD  - Department of Biochemistry and Molecular Biology, Capital Medical University, 
      Beijing, China.
FAU - Qi, Yijun
AU  - Qi Y
AD  - Department of Biochemistry and Molecular Biology, Capital Medical University, 
      Beijing, China.
FAU - Yang, Ying
AU  - Yang Y
AD  - Core Facilities Center, Capital Medical University, Beijing, China.
FAU - Zhang, Yue
AU  - Zhang Y
AD  - Department of Biochemistry and Molecular Biology, Capital Medical University, 
      Beijing, China.
FAU - An, Xinyuan
AU  - An X
AD  - Department of Biochemistry and Molecular Biology, Capital Medical University, 
      Beijing, China.
FAU - Luo, Shudong
AU  - Luo S
AD  - Key Laboratory of Biology of Insect-Pollinator, Ministry of Agriculture, 
      Institute of Apicultural Research, Chinese Academy of Agricultural Sciences, 
      Beijing, China.
FAU - Zheng, Junfang
AU  - Zheng J
AD  - Department of Biochemistry and Molecular Biology, Capital Medical University, 
      Beijing, China.
AD  - Beijing Key Laboratory for Tumor Invasion and Metastasis, Cancer Institute of 
      Capital Medical University, Beijing, China.
LA  - eng
PT  - Journal Article
DEP - 20171117
PL  - United States
TA  - PeerJ
JT  - PeerJ
JID - 101603425
PMC - PMC5695248
OTO - NOTNLM
OT  - Clear cell renal cell carcinoma
OT  - ELK1
OT  - NDUFA4L2
OT  - Transcription factor
COIS- The authors declare there are no competing interests.
EDAT- 2017/11/22 06:00
MHDA- 2017/11/22 06:01
PMCR- 2017/11/17
CRDT- 2017/11/22 06:00
PHST- 2017/03/29 00:00 [received]
PHST- 2017/10/29 00:00 [accepted]
PHST- 2017/11/22 06:00 [entrez]
PHST- 2017/11/22 06:00 [pubmed]
PHST- 2017/11/22 06:01 [medline]
PHST- 2017/11/17 00:00 [pmc-release]
AID - 4065 [pii]
AID - 10.7717/peerj.4065 [doi]
PST - epublish
SO  - PeerJ. 2017 Nov 17;5:e4065. doi: 10.7717/peerj.4065. eCollection 2017.