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Downregulation of m6 A reader YTHDC2 promotes tumor progression and predicts poor prognosis in non-small cell lung cancer.

ABSTRACT: BACKGROUND:m6 A modification affects the pathological progress of many diseases by affecting RNA stability and translocation. YTHDC2, a m6 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).

SUBMITTER: Sun S

PROVIDER: S-EPMC7606000 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Downregulation of m<sup>6</sup> A reader YTHDC2 promotes tumor progression and predicts poor prognosis in non-small cell lung cancer.

Sun Shulei S Han Qiang Q Liang Maoli M Zhang Qian Q Zhang Jing J Cao Jie J

Thoracic cancer 20200921 11

<h4>Background</h4>m<sup>6</sup> A modification affects the pathological progress of many diseases by affecting RNA stability and translocation. YTHDC2, a m<sup>6</sup> A reader, is associated with multiple cancers; however, little is known of its role in non-small cell lung cancer (NSCLC).<h4>Methods</h4>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 ...[more]

PMID: 32956555

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Project description:Background: MEOX1 is a homeobox transcriptional factor, and plays essential roles in regulating somite development. Our previous study indicated that MEOX1 is a critical molecular target in mesenchymal-like cancer cells in PTEN-deficient Trastuzumab resistant breast cancer. Despite the potential implication of MEOX1 for the cancer progression, no previous studies examined its level and clinical significance in lung cancer tissues. In this study, we aimed to detect the MEOX1 expression and correlate its level with clinical outcome in non-small-cell lung cancer patients (NSCLC). Methods: MEOX1 gene expression in lung cancer was examined by using the Oncomine database. MEOX1 protein levels were evaluated by IHC using the corresponding primary antibody on two different commercial lung cancer tissue arrays. siRNA knockdown was used to elucidate the function of MEOX1. Results: Analysis of the Oncomine datasets identified that an elevation of MEOX1 in gene amplification in lung cancer tissues in comparison to normal lung tissues. Immunohistochemistical analysis demonstrated that MEOX1 was localized predominantly in the nucleus, and positive rate was 67.3% (111/165) in NSCLC samples. Statistical analysis revealed high levels of MEOX1 significantly correlated with Lymph Node Metastasis and Stage. Kaplan-Meier survival analysis showed that high levels of MEOX1 were significantly associated with unfavorable survival in NSCLC patients, and MEOX1 nucleus staining had worse survival, than did patients with overall expression in lung squamous cell carcinoma patients. Multivariate Cox's regression analysis found that MEOX1 was an independent poor prognostic predictor for patients with NSCLC. Silencing of MEOX1 by specific SiRNA significantly inhibited H460 and H1299 cell proliferation and sphere formation in serum-free medium. Conclusions: Our results firstly indentified that high levels of MEOX1 especially nuclear staining was an independent prognostic factor for NSCLC, and it served a essential roles in the regulation of cell proliferation and colony formation in vitro. It may represent a potential target for the NSCLC treatment.

Dataset Information

Downregulation of m6 A reader YTHDC2 promotes tumor progression and predicts poor prognosis in non-small cell lung cancer.

Publications

Downregulation of m<sup>6</sup> A reader YTHDC2 promotes tumor progression and predicts poor prognosis in non-small cell lung cancer.

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