Journal of Shanghai Jiao Tong University (Medical Science) >

2021 , Vol. 41 >Issue 4: 434 - 441

DOI: https://doi.org/10.3969/j.issn.1674-8115.2021.04.004

Basic research

USP47 induces cisplatin resistance in head and neck squamous cell carcinoma by up-regulation of anti-apoptotic proteins

  • Tong TONG ,
  • Xing QIN ,
  • Fei XIE ,
  • Ying-ying JIANG ,
  • Jian-bo SHI ,
  • Jian-jun ZHANG
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  • Department of Oral and Maxillofacial-Head & Neck Oncology, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai 200011, China

Received date: 2020-05-12

  Online published: 2021-05-14

Supported by

National Natural Science Foundation of China(81972573);Project of Science and Technology Commission of Shanghai Municipality(18JC1413700);Innovative Research Team of High-Level Local Universities in Shanghai(SSMU-ZLCX20180502)

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Abstract

Objective

· To investigate the effects and underlying mechanism of ubiquitin carboxyl-terminal hydrolase 47 (USP47) on cisplatin resistance in head and neck squamous cells carcinoma (HNSCC).

Methods

· The cisplatin-resistant cell lines of HNSCC were constructed by gradient increase of cisplatin concentration. The expression of USP47 in cisplatin-resistant cell was analyzed by real-time PCR and Western blotting. Stable USP47 over-expressed and silenced USP47 HNSCCs cell lines were generated by lentivirus vector. The influence of the increased or silenced USP47 expression on cisplation resistance were tested by MTT. The influence of USP47 on cell proliferation, colony formation, and apoptosis were examined. Western blotting was performed to detect the expression and ubiquitination levels of X-linked inhibitor of apoptosis protein (XIAP) and recombinant human B-cell lymphoma factor 2 xL (Bcl-xL).

Results

· USP47 expression was significantly increased in cisplatin-resistant cancer cells. Over-expression of USP47 significantly increased the half maximal inhibitory concentration (IC50), while knockout of USP47 gene increased the sensitivity to cisplatin. In addition, the data showed that USP47 expression was negatively related to the proliferation and colony formation abilities of HNSCC cell lines, but it remarkably enhanced the anti-apoptotic effect of HNSCC cells. The protein levels of XIAP and Bcl-xL were significantly elevated in stable USP47 over-expressed cell lines and ubiquitination assay proved that USP47 reduced the ubiquitination levels of XIAP and Bcl-xL proteins. Knockdown of the XIAP and Bcl-xL gene expression blocked cisplatin resistance induced by USP47 gene overexpression.

Conclusion

· USP47 can increase the protein expressions of XIAP and Bcl-xL by inhibiting the ubiquitination modification of them, thereby mediate the cisplatin resistance of HNSCC cells. Inhibition of USP47 expression provides potential application value to reduce cisplatin-resistance during the treatment on HNSCC.

Key words： ubiquitin carboxyl-terminal hydrolase 47 (USP47); cisplatin resistance; head and neck squamous cells carcinoma (HNSCC); X-linked inhibitor of apoptosis protein (XIAP); recombinant human B-cell lymphoma factor 2 xL (Bcl-xL)

Cite this article

Tong TONG , Xing QIN , Fei XIE , Ying-ying JIANG , Jian-bo SHI , Jian-jun ZHANG . USP47 induces cisplatin resistance in head and neck squamous cell carcinoma by up-regulation of anti-apoptotic proteins[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2021 , 41(4) : 434 -441 . DOI: 10.3969/j.issn.1674-8115.2021.04.004

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