Tian Nan, Shangguan Wenbing, Zhou Zuolin, Yao Yao, Fan Chunlei, Cai Lijun
Institute of Molecular Medicine, Life Science College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.
Department of gastroenterology, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.
J Cancer. 2019 Oct 15;10(24):6074-6087. doi: 10.7150/jca.33421. eCollection 2019.
Chemoresistance remains a big challenge in hepatocellular carcinoma (HCC) treatment. Several studies indicated that RNA-binding protein Lin28B serves an oncogenic role in HCC, but its activity in HCC chemotherapy has never been assessed. In this study, we found that overexpression of Lin28B significantly increased the paclitaxel chemoresistance in two different HCC cells lines while silencing Lin28B reduced the chemoresistance in paclitaxel-resistance HCC cells. Curcumin, a natural anti-cancer agent, increased the sensitivity of HCC cells to paclitaxel through inhibiting NF-κB stimulated Lin28B expression both and . Furthermore, by analyzing TCGA (The Cancer Genome Atlas) LIHC (liver hepatocellular carcinoma) and GSE14520 databases, we found that Lin28B was highly upregulated in HCC tissue compared with that in normal tissue and associated with α‑fetoprotein levels, and that patients with Lin28B higher expression had a significant shorter overall survival time than those with Lin28B lower expression. Our data reveal that Lin28B may serve as a predictive biomarker and a treatment target to reverse HCC chemotherapy resistance in future clinical practice.
化疗耐药仍然是肝细胞癌（HCC）治疗中的一大挑战。多项研究表明，RNA结合蛋白Lin28B在HCC中发挥致癌作用，但其在HCC化疗中的活性从未被评估过。在本研究中，我们发现Lin28B的过表达显著增加了两种不同HCC细胞系对紫杉醇的化疗耐药性，而沉默Lin28B则降低了耐紫杉醇HCC细胞的化疗耐药性。姜黄素是一种天然抗癌剂，通过抑制NF-κB刺激的Lin28B表达，增强了HCC细胞对紫杉醇的敏感性。此外，通过分析癌症基因组图谱（TCGA）的肝细胞癌（LIHC）和GSE14520数据库，我们发现与正常组织相比，Lin28B在HCC组织中高度上调，且与甲胎蛋白水平相关，并且Lin28B高表达的患者总生存时间显著短于Lin28B低表达的患者。我们的数据表明，Lin28B可能作为一种预测性生物标志物和治疗靶点，在未来临床实践中逆转HCC化疗耐药性。
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