UBE2L6 is Involved in Cisplatin Resistance by Regulating the Transcription of ABCB6

Author(s): Midori Murakami, Hiroto Izumi*, Tomoko Kurita, Chiho Koi, Yasuo Morimoto, Kiyoshi Yoshino

Journal Name: Anti-Cancer Agents in Medicinal Chemistry
(Formerly Current Medicinal Chemistry - Anti-Cancer Agents)

Volume 20 , Issue 12 , 2020

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Graphical Abstract:


Abstract:

Background: Cisplatin is an important anticancer agent in cancer chemotherapy, but when resistant cells appear, treatment becomes difficult, and the prognosis is poor.

Objective: In this study, we investigated the gene expression profile in cisplatin sensitive and resistant cells, and identified the genes involved in cisplatin resistance.

Methods: Comparison of gene expression profiles revealed that UBE2L6 mRNA is highly expressed in resistant cells. To elucidate whether UBE2L6 is involved in the acquisition of cisplatin resistance, UBE2L6- overexpressing cells established from cisplatin-sensitive cells and UBE2L6-silenced cells developed from cisplatin- resistant cells were generated, and the sensitivity of cisplatin was examined.

Results: The sensitivity of the UBE2L6-overexpressing cells did not change compared with the control cells, but the UBE2L6-silenced cells were sensitized to cisplatin. To elucidate the mechanism of UBE2L6 in cisplatin resistance, we compared the gene expression profiles of UBE2L6-silenced cells and control cells and found that the level of ABCB6 mRNA involved in cisplatin resistance was decreased. Moreover, ABCB6 promoter activity was partially suppressed in UBE2L6-silenced cells.

Conclusion: These results suggest that cisplatin-resistant cells have upregulated UBE2L6 expression and contribute to cisplatin resistance by regulating ABCB6 expression at the transcriptional level. UBE2L6 might be a molecular target that overcomes cisplatin resistance.

Keywords: Cisplatin resistance, ubiquitin-proteasome, ISGylation, ABC transporter, cervical cancer cells, transcription.

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Article Details

VOLUME: 20
ISSUE: 12
Year: 2020
Published on: 07 September, 2020
Page: [1487 - 1496]
Pages: 10
DOI: 10.2174/1871520620666200424130934
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