Lin28/let-7/Bcl-xL pathway: The underlying mechanism of drug resistance in Hep3B cells

Tian,Nan; Han,Ziwu; Li,Zhaohui; Zhou,Mingjie; Fan,Chunlei

doi:10.3892/or.2014.3292

Lin28/let-7/Bcl-xL pathway: The underlying mechanism of drug resistance in Hep3B cells

Authors:
- Nan Tian
- Ziwu Han
- Zhaohui Li
- Mingjie Zhou
- Chunlei Fan
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Affiliations: College of Life Science, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, P.R. China, Department of Neurosurgery, China-Japan Union Hospital, Jilin University, Changchun, Jilin, P.R. China
Published online on: June 25, 2014 https://doi.org/10.3892/or.2014.3292
Pages: 1050-1056

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Abstract

Hepatocellular carcinoma (HCC) is highly resistant to chemotherapeutic drugs, which markedly reduces the effect of chemotherapy. Lin28 has been shown to contribute to tumor relapse after chemotherapy; however, the relationship between Lin28 and chemotherapy drug resistance is unknown. In the present study, we established a drug-resistant Hep3B cell line to investigate the association between Lin28 and drug resistance in HCC, and we identified the underlying mechanisms. We found that the expression of Lin28 was closely associated with resistance to paclitaxel. The drug‑resistant Hep3B cell line, which expresses high levels of Lin28, is more resistant to paclitaxel and other anticancer drugs than the parental cell line. Moreover, further studies showed that dysregulation of Lin28 inhibited let-7 family microRNA levels and upregulated the anti-apoptotic protein Bcl-xL, which is a target of let-7. Our results indicate that the Lin28/let-7/Bcl-xL pathway underlies the drug resistance of Hep3B cells.

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