科研之友
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摘要
Background: The development of drug resistance remains to be a major cause of therapeutic failure in breast cancer patients. How drug-sensitive cells first evade drug inhibition to proliferate remains to be fully investigated. @@@ Methods: Here we characterized the early transcriptional evolution in response to TGF-beta in the human triple-negative breast cells through bioinformatical analysis using a published RNA-seq dataset, for which MCF10A cells were treated with 5 ng/ml TGF-beta 1 for 0 h, 24 h, 48 h and 72 h, and the RNA-seq were performed in biological duplicates. The protein-protein interaction networks of the differentially expressed genes were constructed. KEGG enrichment analysis, cis-regulatory sequence analysis and Kaplan-Meier analysis were also performed to analyze the cellular reprograming induced by TGF-beta and its contribution to the survival probability decline of breast cancer patients. @@@ Result: Transcriptomic analysis revealed that cell growth was severely suppressed by TGF-beta in the first 24 h but this anti-proliferate impact attenuated between 48 h and 72 h. The oncogenic actions of TGF-beta happened within the same time frame with its anti-proliferative effects. In addition, sustained high expression of several drug resistance markers was observed after TGF-beta treatment. We also identified 17 TGF-beta induced genes that were highly correlated with the survival probability decline of breast cancer patients. @@@ Conclusion: Together, TGF-beta plays an important role in tumorigenesis and the development of drug resistance, which implies potential therapeutic strategies targeting the early-stage TGF-beta signaling activities.
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单位1; 广东药学院
