Microarray meta-analysis focused on transcription factors involve in breast cancer cell response to soy isoflavones

Breast cancer is the most common cancer among women and one of the leading causes of cancer deathworldwide. Certain lifestyle behaviors and diet patterns are recognized as factors that influence the risk ofbreast cancer. Intake of phytoestrogens can affect the risk of breast cancer. For the first time, we performedlarge-scale comparative transcriptomic analysis via a meta-analysis of breast cancer cell response to soyisoflavones using microarray gene expression data implemented. By analyzing ۲۸۳ microarray samples from۷ different experiments, we identified ۳,۸۹۰ genes differentially regulated in response to breast cancer cellresponse to soy isoflavones, with a false discovery rate (FDR) ≤ ۰.۰۰۱, of which ۲,۱۷۳ were up-regulatedand ۱,۷۱۷ were down-regulated. Among the DEGs, ۲۶۹ TF genes were identified, and these belong to ۴۲ TFfamilies. The C۲H۲ ZF, bZIP, and bHLH were the largest families with ۸۵, ۲۵, and ۱۹ members, respectively.Recent studies show that zinc finger proteins are key TFs that contribute to cancer progression by regulatingthe transcription of downstream genes involved in proliferation, apoptosis, migration, and invasion. Forexample, ZNF۲۱۷ has been reported to play a critical role in promoting breast cancer metastasis. In total,۵۵.۴% of the TFs were up-regulated and ۴۴.۶% were down-regulated. Interestingly, the expression level ofall TFs in the E۲F family (including E۲F۱-۶, and E۲F۸) were up-regulated in the isoflavones exposurecondition. pRb–E۲F complexes coordinate the expression of genes involved in the cell cycle and apoptosis.Previous studies have indicated that pRb binds to E۲F۱, E۲F۲, and E۲F۳ during much of the G۱ phase of thecell cycle, and it silences gene expression by recruiting HDACs or HMTs. The tumor suppressor pRb exertsits effect on cell growth through interaction with other factors, such as activating E۲F۱-۳.

کلیدواژه ها:

Isoflavones ، Breast cancer ، Transcriptome data ، Meta-analysis