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LncRNA POU3F3 Contributes to Dacarbazine Resistance of Human Melanoma Through the MiR-650/MGMT Axis

Authors :
Kai Wu
Qiang Wang
Yu-Lin Liu
Zhuo Xiang
Qing-Qing Wang
Li Yin
Shun-Li Liu
Source :
Frontiers in Oncology, Vol 11 (2021)
Publication Year :
2021
Publisher :
Frontiers Media S.A., 2021.

Abstract

Background: Alkylating agents are critical therapeutic options for melanoma, while dacarbazine (DTIC)-based chemotherapy showed poor sensitivity in clinical trials. Long non-coding RNAs (lncRNAs) were highlighted in the progression of malignant tumors in recent years, whereas little was known about their involvement in melanoma.Methods: The functional role and molecular mechanism of lncRNA POU3F3 were evaluated on DTIC-resistant melanoma cells. Further studies analyzed its clinical role in the disease progression of melanoma.Results: We observed elevated the expression of lncRNA POU3F3 in the DTIC-resistant melanoma cells. Gain-of-function assays showed that the overexpression of lncRNA POU3F3 maintained cell survival with DTIC treatment, while the knockdown of lncRNA POU3F3 restored cell sensitivity to DTIC. A positive correlation of the expression O6-methylguanine-DNA-methyltransferase (MGMT) was observed with lncRNA POU3F3 in vitro and in vivo. Bioinformatic analyses predicted that miR-650 was involved in the lncRNA POU3F3-regulated MGMT expression. Molecular analysis indicated that lncRNA POU3F3 worked as a competitive endogenous RNA to regulate the levels of miR-650, and the lncRNA POU3F3/miR-650 axis determined the transcription of MGMT in melanoma cells to a greater extent. Further clinical studies supported that lncRNA POU3F3 was a risk factor for the disease progression of melanoma.Conclusion: LncRNA POU3F3 upregulated the expression of MGMT by sponging miR-650, which is a crucial way for DTIC resistance in melanoma. Our results indicated that lncRNA POU3F3 was a valuable biomarker for the disease progression of melanoma.

Details

Language :
English
ISSN :
2234943X and 45975825
Volume :
11
Database :
Directory of Open Access Journals
Journal :
Frontiers in Oncology
Publication Type :
Academic Journal
Accession number :
edsdoj.6c2d485e61164fc0b45975825ad68722
Document Type :
article
Full Text :
https://doi.org/10.3389/fonc.2021.643613