title: Lin28/let-7/Bcl-xL pathway: the underlying mechanism of drug resistance in Hep3B cells.
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.
authors: College of Life Science, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, P.R. China.
authors: Nan
authors: N
authors: Tian
authors: College of Life Science, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, P.R. China.
authors: Ziwu
authors: Z
authors: Han
authors: Department of Neurosurgery, China-Japan Union Hospital, Jilin University, Changchun, Jilin, P.R. China.
authors: Zhaohui
authors: Z
authors: Li
authors: College of Life Science, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, P.R. China.
authors: Mingjie
authors: M
authors: Zhou
authors: College of Life Science, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, P.R. China.
authors: Chunlei
authors: C
authors: Fan
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000235:genetics*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D003520:Cyclophosphamide / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics; D017239:Paclitaxel / Q000494:pharmacology; D016601:RNA-Binding Proteins / Q000235:genetics*; D015854:Up-Regulation; D051020:bcl-X Protein / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; C494811:BCL2L1 protein, human; C000715187:Lin28A protein, human; D035683:MicroRNAs; D016601:RNA-Binding Proteins; D051020:bcl-X Protein; C487931:mirnlet7 microRNA, human; D003520:Cyclophosphamide; D017239:Paclitaxel; D002945:Cisplatin