J Cancer 2019; 10(24):6074-6087. doi:10.7150/jca.33421

Research Paper

Lin28b is involved in curcumin-reversed paclitaxel chemoresistance and associated with poor prognosis in hepatocellular carcinoma

Nan Tian1, Wenbing Shangguan1, Zuolin Zhou1, Yao yao1, Chunlei Fan1, Lijun Cai2✉

1. Institute of Molecular Medicine, Life Science College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
2. Department of gastroenterology, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China

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Citation:
Tian N, Shangguan W, Zhou Z, yao Y, Fan C, Cai L. Lin28b is involved in curcumin-reversed paclitaxel chemoresistance and associated with poor prognosis in hepatocellular carcinoma. J Cancer 2019; 10(24):6074-6087. doi:10.7150/jca.33421. Available from http://www.jcancer.org/v10p6074.htm

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Abstract

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 in vitro and in vivo. 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.

Keywords: curcumin, chemoresistance, Lin28B, NF-κB, hepatocellular carcinoma