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Series GSE83836 Query DataSets for GSE83836
Status Public on Jun 21, 2017
Title TTF-1-regulated miR-532-5p targets KRAS and MKL2 oncogenes and induces apoptosis in lung adenocarcinoma [pts]
Organism Homo sapiens
Experiment type Expression profiling by array
Summary Thyroid transcription factor-1 (TTF-1), also known as NKX2-1, plays a role as a lineage-survival oncogene in lung adenocarcinoma with double-edged sword characteristics. Although previous studies steadily accumulated evidence for roles of TTF-1 in the transcriptional regulation of protein-coding genes, very little is known about its regulatory relationship with miRNAs. In this study, we have identified miR-532-5p as a novel transcriptional target of TTF-1 by an integrative approach, which was designed to extract maximal information from expression profiles of both patient tumors in vivo and TTF-1-inducible cell lines in vitro. Consequently, we have found that miR-532-5p is directly regulated by TTF-1 through its binding to a genomic region 8 kb upstream of miR-532-5p, which appeared to impose transcriptional regulation independent of that of CLCN5, a protein-coding gene harboring miR-532-5p in its intron 3. Further, we have also identified KRAS and MKL2 as novel direct targets of miR-532-5p. Introduction of miR-532-5p mimics markedly induced apoptosis in KRAS-mutant as well as KRAS wildtype lung adenocarcinoma cell lines. Interestingly, miR-532-5p affected the MEK-ERK pathway signaling specifically in cell lines sensitive to siKRAS treatment, while the miR-532-5p-mediated effects were clearly phenocopied by repressing expression or inhibiting function of MKL2 regardless of KRAS mutation status. In summary, our findings demonstrate that miR-532-5p is as novel transcriptional target of TTF-1 and plays a tumor suppressive role by targeting KRAS and MKL2 in lung adenocarcinoma. Novel therapeutic strategies using miR-532-5p or an MKL2 inhibitor may prove effective against this hard-to-cure cancer irrespective of the dependence on KRAS-mediated signaling.
Overall design Microarray analysis using a SurePrint G3 Human GE 8 x 60K ver 2 Microarray G4851B (Agilent) was conducted.
Tumors of 75 lung adenocarcinoma patients which successfully underwent potential curative resection at Aichi Cancer Center, Nagoya, Japan, were investigated.
Contributor(s) Griesing S, Kajino T, Tai MC, Liu Z, Nakatochi M, Shimada Y, Suzuki M, Takahashi T
Citation(s) 28474808
Submission date Jun 29, 2016
Last update date Jan 09, 2018
Contact name Takashi Takahashi
Organization name Aichi Cancer Center
Street address 1-1 Kanokoden, Chikusa-ku
City Nagoya
State/province Aichi
ZIP/Postal code 464-8681
Country Japan
Platforms (1)
GPL17077 Agilent-039494 SurePrint G3 Human GE v2 8x60K Microarray 039381 (Probe Name version)
Samples (75)
GSM2219398 Adenocarcinoma 001
GSM2219399 Adenocarcinoma 002
GSM2219400 Adenocarcinoma 003
This SubSeries is part of SuperSeries:
GSE83839 TTF-1-regulated miR-532-5p targets KRAS and MKL2 oncogenes and induces apoptosis in lung adenocarcinoma
BioProject PRJNA327285

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE83836_RAW.tar 1.6 Gb (http)(custom) TAR (of TXT)
Processed data included within Sample table

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