AUTHOR=Wu Kai , Wang Qiang , Liu Yu-Lin , Xiang Zhuo , Wang Qing-Qing , Yin Li , Liu Shun-Li 

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

JOURNAL=Frontiers in Oncology

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.643613

DOI=10.3389/fonc.2021.643613

ISSN=2234-943X

ABSTRACT=<p><bold>Background:</bold> 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.</p><p><bold>Methods:</bold> 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.</p><p><bold>Results:</bold> 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 <italic>in vitro</italic> and <italic>in vivo</italic>. 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.</p><p><bold>Conclusion:</bold> 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.</p>