LncRNA SLC7A11-AS1 stabilizes CTCF by inhibiting its UBE3A-mediated ubiquitination to promote melanoma metastasis.

ABSTRACT

Malignant melanoma (MM) is one of the most aggressive types of skin cancer. Long non-coding RNAs (lncRNAs) are important regulatory factors in the pathogenesis of various diseases. Here, we found that the lncRNA SLC7A11-AS1 was highly expressed in MM. Therefore, we investigated its regulatory role in the migration and invasion of MM cells and the associated mechanism. SLC7A11-AS1 and CTCF levels in MM cell lines were detected using RT-qPCR and western blotting, and their regulatory effects on the migratory and invasive abilities were determined using CCK-8, EdU, transwell, wound-healing assays and mouse model. RNA pull-down and RIP assays were performed to explore the association of SLC7A11-AS1 and CTCF and the correlation between CTCF and UBE3A. SLC7A11-AS1 and CTCF were highly expressed in MM cells. The knockdown of SLC7A11-AS1 decreased the expression of CTCF. Mechanistically, SLC7A11-AS1 inhibited the degradation of CTCF by inhibiting the ubiquitination by UBE3A. The knockdown of both SLC7A11-AS1 and CTCF inhibited the migration and invasion of MM cells and attenuated MM-to-lung metastasis in a mouse model. Taken together, SLC7A11-AS1 promoted the invasive and migratory abilities of MM cells by inhibiting the UBE3A-regulated ubiquitination of CTCF. Therefore, SLC7A11-AS1 may be a potential therapeutic target for MM.