PMID- 23814265
OWN - NLM
STAT- MEDLINE
DCOM- 20140502
LR  - 20220410
IS  - 1523-5866 (Electronic)
IS  - 1522-8517 (Print)
IS  - 1522-8517 (Linking)
VI  - 15
IP  - 10
DP  - 2013 Oct
TI  - MiR-145 functions as a tumor-suppressive RNA by targeting Sox9 and adducin 3 in 
      human glioma cells.
PG  - 1302-16
LID - 10.1093/neuonc/not090 [doi]
AB  - BACKGROUND: MicroRNAs (miRNAs) are increasingly being recognized as being 
      involved in cancer development and progression in gliomas. METHODS: Using a model 
      cell system developed in our lab to study glioma progression comprising human 
      neuroglial culture (HNGC)-1 and HNGC-2 cells, we report here that miR-145 is one 
      of the miRNAs significantly downregulated during malignant transformation in 
      glioblastoma multiforme (GBM). In a study using tumor samples derived from 
      various glioma grades, we show that expression of miR-145 is decreased in a 
      graded manner, with GBM patients showing lowest expression relative to 
      lower-grade gliomas (P < .05) and normal brain tissues (P < .0001). Functional 
      studies involving ectopic expression of miR-145 in glioma cells had a negative 
      impact on cell proliferation and tumor development, as well as invasion and 
      induced apoptosis, providing further support to the concept that inactivation of 
      miR-145 is important for glioma disease pathogenesis. More notably, these 
      growth-suppressive effects of miR-145 are mediated through its target proteins 
      Sox9 and the cell adhesion-associated molecule adducin 3 (ADD3). RESULTS: 
      Inhibiting Sox9 and ADD3 rescued effects of miR-145 loss. Interestingly, miR-145 
      loss in glioma cells led to overexpression of molecules involved in cell 
      proliferation, like cyclin D1, c-myc, and N-myc, as well as enhanced expression 
      of cell adhesion- and invasion-related molecules N-cadherin and E-cadherin, an 
      effect which was again restored upon miR-145 overexpression in glioma cells. The 
      miR-145 promoter was methylated at its cytosine-phosphate-guanine (CpG) islands 
      in the glioma cell lines studied. CONCLUSION: Our study demonstrates that miR-145 
      has a tumor-suppressive function in glioblastoma in that it reduces 
      proliferation, adhesion, and invasion of glioblastoma cells, apparently by 
      suppressing the activity of oncogenic proteins Sox9 and ADD3. Reduced levels of 
      miR-145 may lead to neoplastic transformation and malignant progression in glioma 
      due to unregulated activity of these proteins.
FAU - Rani, Sandhya B
AU  - Rani SB
AD  - Corresponding Author: Anjali Shiras, MSc, PhD, Scientist-F, National Centre for 
      Cell Science (NCCS), NCCS Complex, University of Pune Campus, Ganeshkhind, Pune 
      411007, Maharashtra, India. anjalishiras@nccs.res.in; anjalishiras@gmail.com.
FAU - Rathod, Sachin Shivaji
AU  - Rathod SS
FAU - Karthik, Shanmuganandam
AU  - Karthik S
FAU - Kaur, Navjot
AU  - Kaur N
FAU - Muzumdar, Dattatraya
AU  - Muzumdar D
FAU - Shiras, Anjali S
AU  - Shiras AS
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130628
PL  - England
TA  - Neuro Oncol
JT  - Neuro-oncology
JID - 100887420
RN  - 0 (ADD3 protein, human)
RN  - 0 (Calmodulin-Binding Proteins)
RN  - 0 (MIRN145 microRNA, human)
RN  - 0 (MicroRNAs)
RN  - 0 (RNA, Messenger)
RN  - 0 (SOX9 Transcription Factor)
RN  - 0 (SOX9 protein, human)
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - Blotting, Western
MH  - Brain Neoplasms/*genetics/metabolism/pathology
MH  - Calmodulin-Binding Proteins/genetics/*metabolism
MH  - Cell Adhesion
MH  - Cell Cycle
MH  - Cell Movement
MH  - Cell Proliferation
MH  - Glioma/*genetics/metabolism/pathology
MH  - Humans
MH  - Mice
MH  - Mice, Inbred NOD
MH  - Mice, SCID
MH  - MicroRNAs/*genetics
MH  - Neoplastic Stem Cells/metabolism/pathology
MH  - RNA, Messenger/genetics
MH  - Real-Time Polymerase Chain Reaction
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - SOX9 Transcription Factor/genetics/*metabolism
PMC - PMC3779040
OTO - NOTNLM
OT  - Sox9
OT  - adducin 3
OT  - glioma stem cells
OT  - invasion
OT  - neoplastic transformation
OT  - promoter methylation
EDAT- 2013/07/03 06:00
MHDA- 2014/05/03 06:00
PMCR- 2014/10/01
CRDT- 2013/07/02 06:00
PHST- 2013/07/02 06:00 [entrez]
PHST- 2013/07/03 06:00 [pubmed]
PHST- 2014/05/03 06:00 [medline]
PHST- 2014/10/01 00:00 [pmc-release]
AID - not090 [pii]
AID - 10.1093/neuonc/not090 [doi]
PST - ppublish
SO  - Neuro Oncol. 2013 Oct;15(10):1302-16. doi: 10.1093/neuonc/not090. Epub 2013 Jun 
      28.