Ranjpour Maryam, Katare Deepshikha P, Wajid Saima, Jain Swatantra K
Department of Biotechnology, School of Chemical and Life Sciences, Jamia Hamdard, New Delhi 110062, India.
Proteomics & Translational Research Lab, Centre for Medical Biotechnology, Institute of Biotechnology, Amity University Uttar Pradesh, Noida, India.
Anticancer Agents Med Chem. 2018;18(8):1163-1176. doi: 10.2174/1871520618666180507141632.
The network interactions link human disease proteins to regulatory cellular pathways leading to better understanding of protein functions and cellular processes. Revealing the network of signaling pathways in cancer through protein-protein interactions at molecular level enhances our understanding of Hepatocellular Carcinoma (HCC).
A rodent model for study of HCC was developed to identify differentially expressed proteins at very early stage of cancer initiation and throughout its progression.
HCC was induced by administrating N-Nitrosodiethylamine (DEN) and 2-aminoacetylfluorine (2-AAF) to male Wistar rats. Proteomic approaches such as 2D-Electrophoresis, PD-Quest, MALDI-TOF-MS and Western blot analyses have been used to identify, characterize and validate the differentially expressed proteins in HCC-bearing animals vis-a-vis controls.
The step-wise analysis of morphological and histological parameters revealed HCC induction and tumorigenesis at 1 and 4 months after carcinogen treatment, respectively. We report a novel protein network of 735 different proteins out of which eight proteins are characterized by MALDI-TOF-MS analysis soon after HCC was chemically induced in rats. We have analyzed four different novel routes representing the association of experimentally identified proteins with HCC progression.
The study suggests that A-Raf, transthyretin and epidermal growth factor receptor play major role in HCC progression by regulating MAPK signaling pathway and lipid metabolism leading to continuous proliferation, neoplastic transformation and tumorigenesis.
网络相互作用将人类疾病蛋白与调节细胞途径联系起来，有助于更好地理解蛋白质功能和细胞过程。通过分子水平的蛋白质-蛋白质相互作用揭示癌症中的信号通路网络，可增强我们对肝细胞癌（HCC）的理解。
建立一种用于研究HCC的啮齿动物模型，以识别癌症起始极早期及整个进展过程中差异表达的蛋白质。
通过给雄性Wistar大鼠施用N-亚硝基二乙胺（DEN）和2-氨基乙酰氟（2-AAF）诱导HCC。已使用二维电泳、PD-Quest、基质辅助激光解吸电离飞行时间质谱（MALDI-TOF-MS）和蛋白质印迹分析等蛋白质组学方法，来识别、表征和验证荷HCC动物相对于对照中差异表达的蛋白质。
对形态学和组织学参数的逐步分析分别显示，在致癌物处理后1个月和4个月时诱导了HCC并发生了肿瘤形成。我们报告了一个由735种不同蛋白质组成的新型蛋白质网络，其中8种蛋白质在大鼠化学诱导HCC后不久通过MALDI-TOF-MS分析进行了表征。我们分析了四条不同的新途径，代表了实验鉴定的蛋白质与HCC进展的关联。
该研究表明，A-Raf、转甲状腺素蛋白和表皮生长因子受体通过调节丝裂原活化蛋白激酶（MAPK）信号通路和脂质代谢，在HCC进展中发挥主要作用，导致持续增殖、肿瘤转化和肿瘤形成。
