LNAPPCC is a novel long non-coding RNA (lncRNA) associated with poor prognosis in colon cancer (CC). However, its dysregulation and consequent effects on tumor progression remain unclear. The expression and subcellular localization of LNAPPCC were determined by qRT-PCR and fluorescence in situ hybridization. The effects of LNAPPCC overexpression and silencing on cell viability, colony formation, lipogenesis, and lipid deposition were evaluated. N6‐methyladenosine (m6A) methylation levels of LNAPPCC were determined using methylated RNA immunoprecipitation (RIP)–PCR. The expression correlation between LNAPPCC and m6A writers (METTL3, METTL14, KIAA1429, and WTAP) was evaluated using two public datasets. Orlistat, an inhibitor of fatty acid synthetase, was used to assess the role of lipogenesis. A dual-luciferase assay was conducted to assess the interaction between METTL3 and LNAPPCC. LNAPPCC was highly expressed in CC cells and primarily located in the nucleus (approximately 70%). LNAPPCC overexpression facilitated cell viability, colony formation, expression of lipogenesis-related enzymes (FASN, ACC1, and SCD1), and increased levels of triglycerides, total cholesterol, free cholesterol, and lipid droplets. These effects were inhibited by LNAPPCC silencing. Orlistat treatment reversed the enhanced viability and colony formation of RKO cells induced by LNAPPCC overexpression. The expression of LNAPPCC was positively correlated with METTL3 in both datasets, and METTL3 interacted with LNAPPCC in the RIP–PCR assay. METTL3-mediated m6A modification of LNAPPCC contributed to the upregulation of LNAPPCC by enhancing its stability. METTL3 silencing inhibited RKO cell viability, colony formation, triglyceride levels, and lipid droplets, whereas METTL3 silencing had no significant effect on the viability and colony formation of RKO cells upon LNAPPCC binding site mutation. LNAPPCC overexpression reversed the anti-tumor effects of METTL3 silencing in vivo. LNAPPCC upregulation promoted lipogenesis in CC, and targeting METTL3-mediated m6A modification on LNAPPCC may be a therapeutic strategy for CC.
Xu et al. (Wed,) studied this question.