Lu Qingchun, Xin Mingyang, Guo Qian, Rothberg Brad S, Gamero Ana M, Yang Ling
Department of Medical Genetics and Molecular Biochemistry, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA.
Noncoding RNA. 2022 Aug 10;8(4):61. doi: 10.3390/ncrna8040061.
The multikinase inhibitor, sorafenib, is a first-line treatment for hepatocellular carcinoma (HCC), but its limited efficacy, drug resistance and toxicity are a concern. In this study, we investigated the role of lncRNA TP53TG1 in the efficacy of sorafenib in HCC cells. We found that treatment with sorafenib increased the expression of TP53TG1 in HCC cells. Knockdown of TP53TG1 sensitized tumor cells to the antiproliferative effects of sorafenib. Furthermore, TP53TG1 knockdown had an additive inhibitory effect on HCC cell proliferation and migration in the presence of sorafenib. The combination of TP53TG1 knockdown and sorafenib drastically inhibited the activation of the ERK pathway. This work demonstrates that TP53TG1 deficiency enhances the efficacy of sorafenib in HCC. Combining TP53TG1 knockdown with sorafenib may be an optimal form of therapy for HCC treatment.
多激酶抑制剂索拉非尼是肝细胞癌（HCC）的一线治疗药物，但其疗效有限、耐药性及毒性令人担忧。在本研究中，我们探究了长链非编码RNA TP53TG1在索拉非尼对HCC细胞疗效中的作用。我们发现，索拉非尼处理可增加HCC细胞中TP53TG1的表达。敲低TP53TG1可使肿瘤细胞对索拉非尼的抗增殖作用敏感。此外，在索拉非尼存在的情况下，敲低TP53TG1对HCC细胞增殖和迁移具有相加抑制作用。敲低TP53TG1与索拉非尼联合可显著抑制ERK通路的激活。这项研究表明，TP53TG1缺失可增强索拉非尼对HCC的疗效。将敲低TP53TG1与索拉非尼联合应用可能是治疗HCC的最佳治疗方式。
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