Department of Hepatobiliary Surgery, The Fifth Affiliated Hospital of Guangxi Medical University, Nanning 530022, Guangxi, China.
Department of Oncology, the People’s Hospital of Binyang County, Binyang 530405, Guangxi, China.
Aging (Albany NY). 2020 Nov 21;12(23):24255-24269. doi: 10.18632/aging.104195.
Sorafenib has long been the only approved systemic therapy for advanced hepatocellular carcinoma (HCC), but most patients show primary or acquired drug resistance. In the present study, RNA was extracted from sorafenib-resistant and -sensitive clones of the HCC cell lines HepG2 and Huh7. Protein-protein interaction networks of the up- and down-regulated genes common to the two sorafenib-resistant cell lines were extracted and subjected to modular analysis in order to identify functional modules. Functional enrichment analysis showed the modules were involved in different biological processes and pathways. These results indicate that sorafenib resistance in HCC is complicated and heterogeneous. The potential regulators of each functional module, including transcription factors, microRNAs and long non-coding RNAs, were explored to construct a comprehensive transcriptional regulatory network related to sorafenib resistance in HCC. Our results provide new insights into sorafenib resistance of HCC at the level of transcriptional regulation.
索拉非尼长期以来一直是晚期肝细胞癌（HCC）唯一批准的系统治疗药物，但大多数患者表现出原发性或获得性药物耐药性。在本研究中，从 HCC 细胞系 HepG2 和 Huh7 的索拉非尼耐药和敏感克隆中提取了 RNA。提取了两个索拉非尼耐药细胞系中共同上调和下调基因的蛋白质-蛋白质相互作用网络，并进行了模块分析，以鉴定功能模块。功能富集分析表明，这些模块参与了不同的生物学过程和途径。这些结果表明 HCC 中的索拉非尼耐药性是复杂和异质的。探索了每个功能模块的潜在调节剂，包括转录因子、microRNAs 和长非编码 RNA，以构建与 HCC 中索拉非尼耐药相关的综合转录调控网络。我们的结果从转录调控水平为 HCC 的索拉非尼耐药性提供了新的见解。
