RNA m6A methyltransferase METTL14 promotes the procession of non‐small cell lung cancer by targeted CSF1R

Abstract

Background Non‐small cell lung cancer (NSCLC) is one of the most malignant cancer types, characterized by a poor prognosis. N6‐methyladenosine (m6A) is a prevalent internal modification of mRNA. METTL14, an RNA methyltransferase that mediates m6A modification, is implicated in mRNA biogenesis. However, the biomechanism of METTL14 in NSCLC is not very clear. Methods Here, immunohistochemical (IHC) assay was employed to detect METTL14 in NSCLC tissues. The biological functions of METTL14 were demonstrated using cell transfection, cell proliferation assay, cell clone formation assay, cell cycle analysis, cell death analysis, transwell and wound healing assays. Transcriptome and methylated RNA immunoprecipitation (MERIP)‐sequencing were used to explore the pathways and potential mechanism of METTL14 in NSCLC. RNA sequencing, METTL14 rip‐sequencing, and METTL14 merip‐sequencing were conducted to identify the potential targets of METTL14. Results METTL14 was significantly correlated with clinical pathological parameters of differentiation and M stage. Additionally, METTL14 promotes cell proliferation, induces cell death, and enhances cell migration and invasion in vitro. Transcriptome and MeRIP‐sequencing reveal oncogenic mechanism of METTL14. RIP‐sequencing highlights CSF1R and AKR1C1 as targets of METTL14. After validation with TCGA dataset, colony stimulating factor 1 receptor (CSF1R) showed significant positive coefficient with METTL14, and was presumed to be one target of METTl14 in lung cancer and verified by the cellular experiments. Conclusion In conclusion, our results revealed the clinical significance of m6A RNA modification atlas, the function, and molecular targets CSF1R of METTL14 in NSCLC cell lines. The RNA m6A methyltransferase METTL14 promotes the progression of NSCLC by targeted CSF1R.

METTL3-mediated m6A modification enhances ZDHHC16 expression in nonsmall- cell lung cancer patients, attenuating ferroptosis by suppressing CREB ubiquitination

“…Previous studies on epigenetics and non-small cell lung cancer have found a close relationship between the two [38,39]. Epigenetic modifications often interfere with the expression and function of normal genes through DNA/ RNA methylation, histone modifications, and changes in the three-dimensional conformation of chromosomes, thereby affecting the occurrence, development, and drug resistance of tumors [40]. Among them, N6 methyladenosine (m6A) is the most common type of RNA modification and plays an important role in tissue development, stem cell self-renewal and differentiation, and tumor resistance [41].…”

Expression patterns and prognostic role of m6A RNA methylation regulators in Non-small Cell Lung Cancer

“…For example, the expression of m6A demethylase ALK-BH5 is upregulated in non-small cell lung cancer stemlike cells, and silencing ALKBH5 inhibits GSC proliferation, thus m6A methylation plays an important role. m6A expression is significantly reduced in non-small cell lung cancer patients, which may be related to the elevated level of FTO and the reduced level of METTL3, suggesting that the m6A regulatory factors are closely related to the occurrence of glioma [9][10][11][12][13]. How to effectively find molecular markers (m6A regulatory factors) to predict the prognosis of NSCLC patients is a problem we need to face.…”

“…The Cancer Genome Atlas (TCGA) is a large-scale genomic analysis of a large number of human tumours, which can be used to identify aberrations at multiple levels of genes, transcripts, proteins and epigenetics, and is increasingly being used to develop new therapeutic approaches [12]. In this study, the TCGA database was used to obtain multi-type histological data and relevant clinical features associated with non-small cell lung cancer.…”