title: Small interfering RNA against transcription factor STAT6 leads to increased cholesterol synthesis in lung cancer cell lines.
abstract: STAT6 transcription factor has become a potential molecule for therapeutic intervention because it regulates broad range of cellular processes in a large variety of cell types. Although some target genes and interacting partners of STAT6 have been identified, its exact mechanism of action needs to be elucidated. In this study, we sought to further characterize the molecular interactions, networks, and functions of STAT6 by profiling the mRNA expression of STAT6 silenced human lung cells (NCI-H460) using microarrays. Our analysis revealed 273 differentially expressed genes after STAT6 silencing. Analysis of the gene expression data with Ingenuity Pathway Analysis (IPA) software revealed Gene expression, Cell death, Lipid metabolism as the functions associated with highest rated network. Cholesterol biosynthesis was among the most enriched pathways in IPA as well as in PANTHER analysis. These results have been validated by real-time PCR and cholesterol assay using scrambled siRNA as a negative control. Similar findings were also observed with human type II pulmonary alveolar epithelial cells, A549. In the present study we have, for the first time, shown the inverse relationship of STAT6 with the cholesterol biosynthesis in lung cancer cells. The present findings are potentially significant to advance the understanding and design of therapeutics for the pathological conditions where both STAT6 and cholesterol biosynthesis are implicated viz. asthma, atherosclerosis etc.
authors.affiliation: Functional Genomics Unit, Institute of Genomics and Integrative Biology (CSIR), Delhi, India.
authors.forename: Richa
authors.initials: R
authors.lastname: Dubey
authors.forename: Ravindresh
authors.initials: R
authors.lastname: Chhabra
authors.forename: Neeru
authors.initials: N
authors.lastname: Saini
mesh_terms: D017304:Annexin A5 / Q000494:pharmacology; D017209:Apoptosis; D002277:Carcinoma / Q000378:metabolism*; D045744:Cell Line, Tumor; D002784:Cholesterol / Q000737:chemistry / Q000378:metabolism*; D019295:Computational Biology / Q000379:methods; D015536:Down-Regulation; D051858:Forkhead Transcription Factors / Q000378:metabolism; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic; D034741:RNA, Small Interfering / Q000378:metabolism*; D050800:STAT6 Transcription Factor / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D017304:Annexin A5; C408469:FOXJ2 protein, human; D051858:Forkhead Transcription Factors; D034741:RNA, Small Interfering; D050800:STAT6 Transcription Factor; D002784:Cholesterol