PMID- 21878637
OWN - NLM
STAT- MEDLINE
DCOM- 20111207
LR  - 20220311
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 286
IP  - 42
DP  - 2011 Oct 21
TI  - MicroRNA-99a inhibits hepatocellular carcinoma growth and correlates with 
      prognosis of patients with hepatocellular carcinoma.
PG  - 36677-85
LID - 10.1074/jbc.M111.270561 [doi]
AB  - In our in-depth analysis carried out by the Illumina Solexa massive parallel 
      signature sequencing, microRNA-99a (miR-99a) was found to be the sixth abundant 
      microRNA in the miRNome of normal human liver but was markedly down-regulated in 
      hepatocellular carcinoma (HCC). Compelling evidence has suggested the important 
      roles of microRNAs in HCC development. However, the biological function of 
      miR-99a deregulation in HCC remains unknown. In this study, we found that miR-99a 
      was remarkably decreased in HCC tissues and cell lines. Importantly, lower 
      miR-99a expression in HCC tissues significantly correlated with shorter survival 
      of HCC patients, and miR-99a was identified to be an independent predictor for 
      the prognosis of HCC patients. Furthermore, restoration of miR-99a dramatically 
      suppressed HCC cell growth in vitro by inducing the G(1) phase cell cycle arrest. 
      Intratumoral injection of cholesterol-conjugated miR-99a mimics significantly 
      inhibited tumor growth and reduced the alpha-fetoprotein level in HCC-bearing nude 
      mice. Insulin-like growth factor 1 receptor (IGF-1R) and mammalian target of 
      rapamycin (mTOR) were further characterized as the direct targets of miR-99a. 
      Furthermore, protein levels of IGF-1R and mTOR were found to be inversely 
      correlated with miR-99a expression in HCC tissues. miR-99a mimics inhibited 
      IGF-1R and mTOR pathways and subsequently suppressed expression of cell 
      cycle-related proteins, including cyclin D1 in HCC cells. Conclusively, miR-99a 
      expression was frequently down-regulated in HCC tissues and correlates with the 
      prognosis of HCC patients, thus proposing miR-99a as a prospective prognosis 
      predictor of HCC. miR-99a suppresses HCC growth by inducing cell cycle arrest, 
      suggesting miR-99a as potential tumor suppressor for HCC therapeutics.
FAU - Li, Dong
AU  - Li D
AD  - Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, 
      China.
FAU - Liu, Xingguang
AU  - Liu X
FAU - Lin, Li
AU  - Lin L
FAU - Hou, Jin
AU  - Hou J
FAU - Li, Nan
AU  - Li N
FAU - Wang, Chunmei
AU  - Wang C
FAU - Wang, Pin
AU  - Wang P
FAU - Zhang, Qian
AU  - Zhang Q
FAU - Zhang, Peng
AU  - Zhang P
FAU - Zhou, Weiping
AU  - Zhou W
FAU - Wang, Zhengxin
AU  - Wang Z
FAU - Ding, Guoshan
AU  - Ding G
FAU - Zhuang, Shi-Mei
AU  - Zhuang SM
FAU - Zheng, Limin
AU  - Zheng L
FAU - Tao, Wenzhao
AU  - Tao W
FAU - Cao, Xuetao
AU  - Cao X
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110830
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (MIRN99 microRNA, human)
RN  - 0 (MicroRNAs)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (RNA, Neoplasm)
RN  - 0 (alpha-Fetoproteins)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Carcinoma, Hepatocellular/diagnosis/genetics/*metabolism/therapy
MH  - *Cell Cycle Checkpoints
MH  - Down-Regulation/genetics
MH  - Female
MH  - *G1 Phase
MH  - *Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Liver Neoplasms/diagnosis/genetics/*metabolism/therapy
MH  - Male
MH  - MicroRNAs/*biosynthesis/genetics
MH  - Middle Aged
MH  - Neoplasm Proteins/genetics/metabolism
MH  - Prognosis
MH  - RNA, Neoplasm/*biosynthesis/genetics
MH  - TOR Serine-Threonine Kinases/genetics/metabolism
MH  - alpha-Fetoproteins/genetics/metabolism
PMC - PMC3196113
EDAT- 2011/09/01 06:00
MHDA- 2011/12/13 00:00
PMCR- 2012/10/21
CRDT- 2011/09/01 06:00
PHST- 2011/09/01 06:00 [entrez]
PHST- 2011/09/01 06:00 [pubmed]
PHST- 2011/12/13 00:00 [medline]
PHST- 2012/10/21 00:00 [pmc-release]
AID - S0021-9258(20)50866-1 [pii]
AID - M111.270561 [pii]
AID - 10.1074/jbc.M111.270561 [doi]
PST - ppublish
SO  - J Biol Chem. 2011 Oct 21;286(42):36677-85. doi: 10.1074/jbc.M111.270561. Epub 
      2011 Aug 30.