Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Increased miR-708 expression in NSCLC and its association with poor survival in lung adenocarcinoma from Never Smokers

ABSTRACT: We demonstrate that miR-708 is one of the most highly overexpressed miRNAs in non-small cell lung cancer. High level of miR-708 in tumor is also associated with a reduced overall survival in lung adenocarcinomas from never smokers. Functionally, miR-708 overexpression increases the proliferation, migration, and invasion in cultured cells and down regulates TMEM88, a negative regulator of Wnt signaling. Jointly, our results support an oncogenic role of miR-708 by activating Wnt signaling pathway to promote lung cancer progression. We performed miRNA expression profiling in matched lung adenocarcinoma and uninvolved lung using 47 pairs from formalin-fixed, paraffin-embedded [FFPE] tissues from never smokers. We performed miRNA expression profiling in matched lung adenocarcinoma and uninvolved lung using 56 pairs of fresh-frozen [FF] samples from never smokers.

ORGANISM(S): Homo sapiens

SUBMITTER: Jin Sung Jang

PROVIDER: E-GEOD-36681 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Increased miR-708 expression in NSCLC and its association with poor survival in lung adenocarcinoma from never smokers.

Jang Jin Sung JS Jeon Hyo-Sung HS Sun Zhifu Z Aubry Marie Christine MC Tang Hui H Park Cheol-Hong CH Rakhshan Fariborz F Schultz Debra A DA Kolbert Christopher P CP Lupu Ruth R Park Jae Yong JY Harris Curtis C CC Yang Ping P Jen Jin J

Clinical cancer research : an official journal of the American Association for Cancer Research 20120509 13

<h4>Purpose</h4>miRNA plays an important role in human disease and cancer. We seek to investigate the expression status, clinical relevance, and functional role of miRNA in non-small cell lung cancer.<h4>Experimental design</h4>We conducted miRNA expression profiling in matched lung adenocarcinoma and uninvolved lung using 56 pairs of fresh-frozen (FF) and 47 pairs of formalin-fixed, paraffin-embedded (FFPE) samples from never smokers. The most differentially expressed miRNA genes were evaluated ...[more]

PMID: 22573352

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Project description:Approximately 15% of lung cancer cases are not associated with smoking and show molecular and clinical characteristics distinct from those in smokers. Epidermal growth factor receptor (EGFR) gene mutations, which are correlated with sensitivity to EGFR-tyrosine kinase inhibitors (EGFR-TKIs), are more frequent in never-smoker lung cancers. In this study, microRNA (miRNA) expression profiling of 28 never-smoker lung cancer cases identified aberrantly expressed miRNAs, which were much fewer than in lung cancers of smokers and included miRNAs previously identified (e.g., upregulated miR-21) and unidentified (e.g., downregulated miR-138) in those smoker cases. The changes in expression of some of these miRNAs were more remarkable in cases with EGFR mutations than in those without: the most upregulated miRNA, miR-21, was more abundant in cancers with EGFR mutation. A significant correlation between phosphorylated-EGFR (p-EGFR) and miR-21 levels in lung carcinoma cell lines and the suppression of miR-21 by an EGFR-TKI, AG1478, suggested that the EGFR signaling pathway positively regulated miR-21 expression. In a never-smoker-derived lung adenocarcinoma cell line H3255 with mutant EGFR and high levels of p-EGFR and miR-21, antisense inhibition of miR-21 enhanced AG1478-induced apoptosis. In a never-smoker-derived adenocarcinoma cell line H441 with wild-type EGFR, the antisense miR-21 not only showed the additive effect with AG1478 but also induced apoptosis by itself. These results suggest that aberrantly increased expression of miR-21, which is further enhanced by the activated EGFR signaling pathway, plays a critical role in lung carcinogenesis in never-smokers and is a potential therapeutic target in both EGFR mutant and wild-type cases. Twenty-eight pairs of lung cancer tissues and corresponding noncancerous lung tissues were obtained from never-smokers who had undergone surgical resection from 2000 to 2004 at the University of Maryland Medical Center (n=15), Mayo Clinic (n=7) in United States and Hamamatsu University School of Medicine (n=6) in Japan.

Dataset Information

Increased miR-708 expression in NSCLC and its association with poor survival in lung adenocarcinoma from Never Smokers

Publications

Increased miR-708 expression in NSCLC and its association with poor survival in lung adenocarcinoma from never smokers.

Similar Datasets

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