PMID- 23173671
OWN - NLM
STAT- MEDLINE
DCOM- 20130523
LR  - 20220317
IS  - 1471-2407 (Electronic)
IS  - 1471-2407 (Linking)
VI  - 12
DP  - 2012 Nov 23
TI  - MicroRNA-99a induces G1-phase cell cycle arrest and suppresses tumorigenicity in 
      renal cell carcinoma.
PG  - 546
LID - 10.1186/1471-2407-12-546 [doi]
AB  - BACKGROUND: A growing body of evidence suggests that microRNAs (miRNAs) play an 
      important role in cancer diagnosis and therapy. MicroRNA-99a (miR-99a), a 
      potential tumor suppressor, is downregulated in several human malignancies. The 
      expression and function of miR-99a, however, have not been investigated in human 
      renal cell carcinoma (RCC) so far. We therefore examined the expression of 
      miR-99a in RCC cell lines and tissues, and assessed the impact of miR-99a on the 
      tumorigenesis of RCC. METHODS: MiR-99a levels in 40 pairs of RCC and matched 
      adjacent non-tumor tissues were assessed by real-time quantitative Reverse 
      Transcription PCR (qRT-PCR). The RCC cell lines 786-O and OS-RC-2 were 
      transfected with miR-99a mimics to restore the expression of miR-99a. The effects 
      of miR-99a were then assessed by cell proliferation, cell cycle, transwell, and 
      colony formation assay. A murine xenograft model of RCC was used to confirm the 
      effect of miR-99a on tumorigenicity in vivo. Potential target genes were 
      identified by western blotting and luciferase reporter assay. RESULTS: We found 
      that miR-99a was remarkably downregulated in RCC and low expression level of 
      miR-99a was correlated with poor survival of RCC patients. Restoration of miR-99a 
      dramatically suppressed RCC cells growth, clonability, migration and invasion as 
      well as induced G1-phase cell cycle arrest in vitro. Moreover, intratumoral 
      delivery of miR-99a could inhibit tumor growth in murine xenograft models of 
      human RCC. In addition, we also fond that mammalian target of rapamycin (mTOR) 
      was a direct target of miR-99a in RCC cells. Furthermore, siRNA-mediated 
      knockdown of mTOR partially phenocopied the effect of miR-99a overexpression, 
      suggesting that the tumor suppressive role of miR-99a may be mediated primarily 
      through mTOR regulation. CONCLUSIONS: Collectively, these results demonstrate for 
      the first time, to our knowledge, that deregulation of miR-99a is involved in the 
      etiology of RCC partially via direct targeting mTOR pathway, which suggests that 
      miR-99a may offer an attractive new target for diagnostic and therapeutic 
      intervention in RCC.
FAU - Cui, Li
AU  - Cui L
AD  - Department of Urology, The Third Affiliated Hospital of Soochow University, 185 
      Juqian Street, Changzhou, 213003, China.
FAU - Zhou, Hua
AU  - Zhou H
FAU - Zhao, Hu
AU  - Zhao H
FAU - Zhou, Yaojun
AU  - Zhou Y
FAU - Xu, Renfang
AU  - Xu R
FAU - Xu, Xianlin
AU  - Xu X
FAU - Zheng, Lu
AU  - Zheng L
FAU - Xue, Zhong
AU  - Xue Z
FAU - Xia, Wei
AU  - Xia W
FAU - Zhang, Bo
AU  - Zhang B
FAU - Ding, Tao
AU  - Ding T
FAU - Cao, Yunjie
AU  - Cao Y
FAU - Tian, Zinong
AU  - Tian Z
FAU - Shi, Qianqian
AU  - Shi Q
FAU - He, Xiaozhou
AU  - He X
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20121123
PL  - England
TA  - BMC Cancer
JT  - BMC cancer
JID - 100967800
RN  - 0 (3' Untranslated Regions)
RN  - 0 (MIRN99 microRNA, human)
RN  - 0 (MicroRNAs)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
EIN - BMC Cancer. 2021 Jan 29;21(1):103. PMID: 33514330
MH  - 3' Untranslated Regions/genetics
MH  - Animals
MH  - Blotting, Western
MH  - Carcinoma, Renal Cell/*genetics/pathology/prevention & control
MH  - Cell Line
MH  - Cell Line, Tumor
MH  - Cell Movement/genetics
MH  - Cell Proliferation
MH  - Down-Regulation
MH  - G1 Phase Cell Cycle Checkpoints/*genetics
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Kaplan-Meier Estimate
MH  - Kidney Neoplasms/*genetics/pathology/prevention & control
MH  - Mice
MH  - Mice, Nude
MH  - MicroRNAs/administration & dosage/*genetics
MH  - RNA Interference
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - TOR Serine-Threonine Kinases/genetics/metabolism
MH  - Transfection
MH  - Xenograft Model Antitumor Assays
PMC - PMC3518250
EDAT- 2012/11/24 06:00
MHDA- 2013/05/25 06:00
PMCR- 2012/11/23
CRDT- 2012/11/24 06:00
PHST- 2012/08/31 00:00 [received]
PHST- 2012/11/19 00:00 [accepted]
PHST- 2012/11/24 06:00 [entrez]
PHST- 2012/11/24 06:00 [pubmed]
PHST- 2013/05/25 06:00 [medline]
PHST- 2012/11/23 00:00 [pmc-release]
AID - 1471-2407-12-546 [pii]
AID - 10.1186/1471-2407-12-546 [doi]
PST - epublish
SO  - BMC Cancer. 2012 Nov 23;12:546. doi: 10.1186/1471-2407-12-546.