Downregulation of m⁶A reader YTHDC2 promotes tumor progression and predicts poor prognosis in non‐small cell lung cancer

Abstract

Background m 6 A modification affects the pathological progress of many diseases by affecting RNA stability and translocation. YTHDC2, a m 6 A reader, is associated with multiple cancers; however, little is known of its role in non‐small cell lung cancer (NSCLC). Methods The GEPIA, Oncomine and GEO databases were analyzed to assess expression of YTHDC2 in NSCLC patients. Quantitative polymerase chain reaction, western blot and immunohistochemistry were used to detect YTHDC2 expression in different NSCLC cell lines (H1299, H460, H292 and A549) and patients. The effects of YTHDC2 on NSCLC cell lines (A549 and H1299) proliferation and migration were employed using CCK8 and transwell assays. The potential target RNAs of YTHDC2 were obtained from the POSTAR database. Functional enrichment analysis of YTHDC2 targeted RNAs was performed using the Metascape database. Results GEPIA, Oncomine and GEO databases showed low expression of YTHDC2 in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) patients. YTHDC2 expression was significantly decreased in different NSCLC cell lines and our clinical samples. Moreover, low expression of YTHDC2 was significantly associated with poor differentiation, lymph node metastasis, tumor size and stage. In addition, YTHDC2 could suppress the proliferation and migration ability of A549 and H1299 cell lines. Kaplan‐Meier Plotter database analysis revealed that patients with low level of YTHDC2 had a significantly poor prognosis. Finally, functional enrichment analysis of YTHDC2 targeted RNAs indicated several enriched pathways related to cancer. Conclusions These findings elucidate that YTHDC2 suppresses tumorigenesis in NSCLC, indicating that YTHDC2 may be a promising therapeutic target for NSCLC. Key points Significant findings of the study This study demonstrated that the downregulation of YTHDC2 promotes tumor progression and predicts poor prognosis in non‐small cell lung cancer (NSCLC). What this study adds YTHDC2 might be a promising therapeutic target for non‐small cell lung cancer (NSCLC).

m6A Regulators Is Differently Expressed and Correlated With Immune Response of Esophageal Cancer

“…In addition, knocking down hnRNPA2B1 can inhibit ESCA growth and metastasis ( Guo et al, 2020 ). In non-small cell lung cancer, down-regulation of the m6A reader YTHDC2 promotes tumor progression and predicts poor prognosis ( Sun et al, 2020 ). YTHDC2 activates the IGF1R/Akt/S6 signal axis to promote radiotherapy tolerance for nasopharyngeal carcinoma ( He et al, 2020 ).…”

Identification of the Signature Associated With m6A RNA Methylation Regulators and m6A-Related Genes and Construction of the Risk Score for Prognostication in Early-Stage Lung Adenocarcinoma

“…In a mouse model, low YTHDC2 expression was associated with poor prognosis in LUAD patients, and YTHDC2 improves the prognosis of LUAD patients by inhibiting the independent antioxidant function of SLC7A11 (Ma et al, 2021). In non-small cell lung cancer, a research analyzed a series of publicly available online databases and found that low YTHDC2 expression was associated with lymph node metastasis and poor prognosis (Sun et al, 2020).…”

“…We then reviewed the proteomic data and found YTHDC2 protein was reported significantly underexpressed in non-small cell lung cancer (Sun et al, 2020). The representative protein expression of ADH1C and YTHDC2 was explored in the human protein profiles and is shown in Figure 5B.…”

Role of RNA N6-Methyladenosine Modification in Male Infertility and Genital System Tumors

“…In lung adenocarcinoma, it suppresses the tumorigenesis and development by inhibiting SLC7A11-dependent antioxidant function ( Ma et al, 2021 ). In non-small cell lung cancer, downregulation of m6A reader YTHDC2 promotes tumor progression and predicts poor prognosis ( Sun S. et al, 2020 ). YTHDC2 may promote the metastasis of colon cancer by promoting the translation of HIF-1α, and YTHDC2 may be a diagnostic marker and target gene for the treatment of colon cancer ( Tanabe et al, 2016 ).…”