LINC01278 Induces Autophagy to Inhibit Tumour Progression by Suppressing the mTOR Signalling Pathway

Abstract

Uveal melanoma (UM) is an aggressive intraocular malignant tumour that is closely related to autophagic dysfunction. We aimed to identify autophagy-related long noncoding RNAs (lncRNAs) to elucidate the molecular mechanism of UM. Here, we show that LINC01278 is a new potential biomarker with clinical prognostic value in UM through bioinformatics analysis. Application of an autophagy inhibitor (3-MA) and an autophagy agonist (MG-132) indicated that LINC01278 can inhibit UM cell proliferation, migration, and invasion by inducing autophagy. A xenograft nude mouse model was used to examine the tumorigenesis of UM cells in vivo. Mechanistically, LINC01278 can inhibit the mTOR signalling pathway to activate autophagy, as shown by experiments with an mTOR agonist (MHY1485) and mTOR inhibitor (rapamycin) treatment. Our findings indicate that LINC01278 functions as a tumour suppressor by inhibiting the mTOR signalling pathway to induce autophagy. Targeting the LINC01278-mTOR axis might be a novel and promising therapeutic approach for UM.

The multiple roles of autophagy in uveal melanoma and the microenvironment

“…LINC01278 is lowly expressed in UM, and the tumour patients with high expression of LINC01278 have a better prognosis. Meanwhile, LINC01278 inhibited the development of UM by activating autophagy, which was also demonstrated by in vitro experiments (Liu et al 2023a ). D-type cyclins (CCNDs), among the most often dysregulated therapeutic targets in human cancer, play a crucial role in regulating the cell division cycle.…”

The Role of Autophagy in Human Uveal Melanoma and the Development of Potential Disease Biomarkers and Novel Therapeutic Paradigms

“…This finding was also translated onto xenograft mouse models where upregulation of LINC01278 reduced the volume and weight of tumour compared to control. With these as the basis, more research into the insight of the function and use of LnRNA is encouraged to uncover potential diagnostics and treatment options for UM [107].…”

Recent Advances in Molecular and Genetic Research on Uveal Melanoma

“…Additional evidence points to six specific autophagy-linked lncRNAs that exhibited differential expression in UM cell lines with lncRNAs, SOS1-IT1, AC016747.1, AC100791.3 and AC018904.1 acting as risk factors, whereas AC104825.1 and AC090617.5 serving as protective elements [ 172 ]. Lower expression of LINC01278 was linked to high-risk UMs and suppressed the proliferation, migration and invasion of UM cells by promoting autophagy [ 173 ].…”