METTL14-mediated m6A modification of LINC00340 exerts oncogenic role in retinoblastoma by regulating Notch signaling pathway.

Abstract

Purpose: Retinoblastoma (RB) is a common primary intraocular cancer developed in early childhood. The N6-methyladenosine (m⁶A) modification of long non-coding RNAs (lncRNAs) have been reported to participate in tumorigenesis. However, the study on the m⁶A modification of lncRNA in RB is still limited. This study proposed to reveal the role of lncRNA LINC00340 in RB depending on m⁶A modification.

Methods: The levels of LINC00340 and methyltransferase-like 14 (METTL14) were detected using qRT-PCR. The effects of LINC00340 interacting with METTL14 on RB cells were assessed by CCK8, colony formation, and flow cytometry assays. The changes of proteins associated with Notch signaling pathway were detected using western blotting. The regulatory mechanism of LINC00340 interacting with METTL14 in RB cells was confirmed by MeRIP, qRT-PCR, and actinomycin D treatment assays.

Results: The expression of LINC00340 and METTL14 in RB samples were elevated, as well as their levels in RB samples showed the positive correlation. Silencing LINC00340 in RB cells could impair RB cell growth and enhance apoptosis via activating Notch signaling pathway, but overexpressing LINC00340 in RB cells showed the opposite effects. In addition, upregulating METTL14 effectively relieved the repressive effects of silencing LINC00340 on RB cells due to METTL14-mediated m⁶A modification of LINC00340.

Conclusions: The findings of study reveal that METTL14-mediated m⁶A modification of LINC00340 exerts oncogenic function in RB via Notch signaling pathway, which may uncover a novel molecular mechanism driving RB progression and identify a potential therapeutic target for RB.