Chemotherapy resistance is still a key hurdle in current hepatocellular carcinoma (HCC) treatment. Therefore, clarifying the molecular mechanisms contributing to this acquired resistance is urgent for the effective treatment of liver cancer. In this research, we observed that lncRNA FAM225A expression is dramatically upregulated not only in hepatocellular carcinoma tissues and cell lines but also in sorafenib-resistant HepG2/SOR cells. Moreover, FAM225A knockdown significantly weakened HepG2/SOR cells resistance to sorafenib treatment by MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Similar results were obtained from the tumor xenograft model in mice. Further mechanistic researches revealed that the direct interaction between FAM225A and miR-130a-5p, while miR-130a-5p negatively modulated CCNG1 expression by targeting 3'UTR of CCNG1. MiR-130a-5p inhibition or CCNG1 overexpression could partially offset FAM225A knockdown-induced increased viability of HepG2/SOR cells in response to sorafenib challenge. Collectively, our findings provide evidence that FAM225A/miR-130a-5p/CCNG1 interaction network regulates the resistance of HCC cells to sorafenib treatment and could supply a possible strategy for restoring sorafenib sensitivity in HCC therapy.

中文翻译：

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FAM225A通过调节miR-130a-5p-CCNG1相互作用网络来促进肝癌细胞索拉非尼耐药。

化疗耐药性仍然是当前肝细胞癌（HCC）治疗的关键障碍。因此，弄清促成这种获得性耐药的分子机制对于有效治疗肝癌迫在眉睫。在这项研究中，我们观察到lncRNA FAM225A的表达不仅在肝细胞癌组织和细胞系中而且在对索拉非尼耐药的HepG2 / SOR细胞中都显着上调。此外，FAM225A敲低大大减弱了HepG2 / SOR细胞对MTT（3-（4,5-Dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide）索拉非尼治疗的抵抗力。从小鼠的肿瘤异种移植模型获得了相似的结果。进一步的机理研究表明，FAM225A与miR-130a-5p之间存在直接的相互作用，而miR-130a-5p通过靶向CCNG1的3'UTR负调控CCNG1的表达。MiR-130a-5p抑制或CCNG1过表达可以部分抵消FAM225A敲低诱导的对索拉非尼激发的HepG2 / SOR细胞活力的增加。总的来说，我们的发现提供了证据，即FAM225A / miR-130a-5p / CCNG1相互作用网络调节HCC细胞对索拉非尼治疗的耐药性，并可能为恢复索拉非尼在HCC治疗中的敏感性提供可能的策略。