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

Abstract

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

Identification of a novel glycolysis-related gene signature for predicting the prognosis of osteosarcoma patients

“…ABCB6, an ATP-binding cassette (ABC) transporter group member, is one of the hallmark genes in glycolysis. There are many biological effects of ABCB6, such as protection against oxidative stress [ 31 ], acquired resistance [ 32 , 33 ], and the potential promotion of tumor proliferation [ 34 , 35 ]. Consistently, our results showed that ABCB6 was overexpressed in patients with metastatic OS and a high expression of ABCB6 indicated a low survival rate in OS patients.…”

Association of the Epithelial–Mesenchymal Transition (EMT) with Cisplatin Resistance

“…CP is a key member of platinum compounds with excellent anti-tumor activity against different cancers such as breast cancer, prostate cancer, bladder cancer, lung cancer, brain tumors, and so on [21][22][23]. The rational reasons for selection of CP are as follows: (1) its anti-tumor activity has been extensively examined, particularly in clinical trials [24][25][26], and (2) the molecular mechanisms and pathways involved in CP resistance/sensitivity have been explored [27][28][29]. Consequently, it has been possible to implicate the process of EMT in drug resistance and directing further studies towards targeting EMT in suppressing resistance developed against CP treatment.…”

Ubiquitin Proteasome Pathway Transcriptome in Epithelial Ovarian Cancer

“…UBE2L6 has been found to be associated with autophagy in esophageal cancer [ 55 ] but has not been previously associated with EOC. Murakami et al [ 56 ] found that cisplatin-resistant cervical cancer cells had overexpressed levels of UBE2L6. While we found no association of UBE2L6 with EOC in the literature, the association with cisplatin sensitivity makes it relevant to the treatment of chemoresistant HGSOC.…”