TRMT10C-Induced m1A Methylation Decreases HMGN2 Expression to Advance Lung Cancer Progression

Abstract

Background: This study investigated the role of tRNA methyltransferase 10C (TRMT10C) and the mechanism of N¹-methyladenosine (m¹A) methylation modification in lung cancer (LC). Methods: Western blot and quantitative reverse transcription polymerase chain reaction (qRT-PCR) were used to measure high mobility group nucleosomal binding domain 2 (HMGN2) expression in LC cells. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometry and tube formation assay were utilized to assess the cell viability, angiogenesis, and apoptosis, respectively. m¹A-qRT-PCR was engineered to elucidate the impacts of m¹A methylation related genes (TRMT10C, alkB homolog 1 (ALKBH1), and ALKBH3) upon the m¹A methylation of HMGN2 in LC cells. StarBase, along with Kaplan-Meier Plotter, was used to test TRMT10C expression in LC and find out its correlation with the survival of LC patients. Cell function assays were operated again to identify the role of TRMT10C in LC cells. Results: There was a low expression of HMGN2 in LC cells, but TRMT10C expression was increased in LC. Kaplan-Meier Plotter website showed that high expression of TRMT10C was coupled with the low survival of LC patients (logrank p = 1.2 × 10^-8). After that, the m¹A methylation of HMGN2 was induced in LC cells and enhanced by TRMT10C overexpression. In addition, TRMT10C overexpression increased the cell viability and angiogenesis rate while suppressing apoptosis and HMGN2 expression. Its effects were counteracted by overexpressed HMGN2. Conclusion: TRMT10C augments the malignant phenotype of LC by increasing m¹A methylation modification of HMGN2.