Genes ingenuity pathway analysis unveils smoothelin‐like 1 (SMTNL1) as a key regulatory protein involved in sodium pentobarbital‐induced growth inhibition in breast cancer
Bingwei Li, Xiaoyan Zhang, Xueting Liu, Ailing Li, Jianqun Han
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引用次数: 0
Abstract
Abstract We previously reported that sodium pentobarbital inhibited the growth of the breast cancer associated with the normalization of microcirculatory hemodynamics and oxygenation. Here, we aimed to screen the key regulatory proteins involved in pentobarbital‐induced normalization of microcirculatory hemodynamics in the breast cancer tissues. A nude mice model of xenograft was established using triple negative breast cancer cell line MDA‐MB‐231. After tumor cell implantation, the mice were subcutaneously injected with 50 mg/kg/day of sodium pentobarbital or an equal volume of solvent adjacent to the tumor for 14 days. Liquid chromatography linked to tandem mass spectrometry (LC–MS/MS) was used to analyze the difference in protein expression profile between the two groups. Ingenuity pathway analysis (IPA) was used to perform the canonical pathway analysis, upstream regulators analysis, and protein–protein interaction networks analysis. Screened proteins were confirmed by real‐time quantitative polymerase chain reaction (RT–qPCR) and Western blot analysis. A total of 101 differentially expressed proteins were revealed between groups. Canonical pathway analysis suggested that acute phase response signaling ( z = 1, p = .00208), dilated cardiomyopathy signaling pathway ( z = −2, p = .00671), and ILK signaling ( z = 1, p = .0172) were key pathways with highlight associations. The mRNA and protein expressions of SMTNL1 were found significantly decreased in pentobarbital‐treated tumor tissues compared with those in controls (both p < .01). Nine important protein–protein interaction networks were identified, and of which, two contained multiple downstream regulatory proteins of SMTNL1. In conclusion, SMTNL1 is revealed as a key protein involved in pentobarbital‐induced growth inhibition signaling in breast cancer. SMTNL1 may become a new potential target for tumor microcirculation research.
期刊介绍:
PR&P is jointly published by the American Society for Pharmacology and Experimental Therapeutics (ASPET), the British Pharmacological Society (BPS), and Wiley. PR&P is a bi-monthly open access journal that publishes a range of article types, including: target validation (preclinical papers that show a hypothesis is incorrect or papers on drugs that have failed in early clinical development); drug discovery reviews (strategy, hypotheses, and data resulting in a successful therapeutic drug); frontiers in translational medicine (drug and target validation for an unmet therapeutic need); pharmacological hypotheses (reviews that are oriented to inform a novel hypothesis); and replication studies (work that refutes key findings [failed replication] and work that validates key findings). PR&P publishes papers submitted directly to the journal and those referred from the journals of ASPET and the BPS