YTHDF2 suppresses cell proliferation and growth via destabilizing the EGFR mRNA in hepatocellular carcinoma

Zhong, Li; Liao, Dan; Zhang, Meifang; Zeng, Cuiling; Li, Xinchun; Zhang, Ruhua; Ma, Hu; Kang, Tiebang

doi:10.1016/j.canlet.2018.11.006

Cited by 280 publications

(262 citation statements)

References 38 publications

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“…The three genes (YTHDC2, YTHDF2, and METTL3) incorporated in the prognosis risk model were upregulated in the LC patients in both LIRI-JP and LIHC datasets, which are similar to those of previous studies (Yuan et al, 2014;Chen et al, 2018). YTHDF2 and METTL3 have previously been reported as tumor suppressors in HCC, and as oncogenes in pancreatic cancer and acute myelocytic leukemia (Cui et al, 2017;Wang et al, 2017; Zhong et al, 2019). Chen et al (2018) demonstrated that overexpression of METTL3 in HCC patients have poor prognosis.…”

Section: Discussionsupporting

confidence: 84%

“…Further, knockout of METTL3 suppresses HCC tumorigenicity and lung metastasis by modulation of cytokine signaling 2 through a YTHDF2-dependent mechanism . Zhong et al (2019) demonstrated that YTHDF2 acts as an HCC suppressor via promoting the degradation of epidermal growth factor receptor mRNA. Hou et al (2019) reported that a high expression of YTHDF2 gives rise to a better prognosis of HCC patients, and represses tumor growth and angiogenesis by degradation of interleukin 11 and serpin family E member 2 mRNAs.…”

Section: Discussionmentioning

confidence: 99%

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RNA N6-Methyladenosine-Related Gene Contribute to Clinical Prognostic Impact on Patients With Liver Cancer

et al. 2020

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Liver cancer (LC) is the fourth leading cause of cancer-related deaths worldwide. There is an urgent need to identify novel and reliable prognostic biomarkers for LC in order to improve patient outcomes. N6-methyladenosine (m6A) is the most common internal modification in eukaryotic mRNA and has been associated with various cancers, although its roles in the prognosis of LC remains to be elucidated. We analyzed the expression profiles of 15 m6A-related genes in the International Cancer Genome Consortium (ICGC) LIRI-JP dataset, and applied consensus clustering to stratify LC patients into two subgroups (Cluster 1 and Cluster 2). Cluster1 was significantly correlated to lower tumor stage and longer overall survival (OS). Gene set enrichment analysis showed that tumorigenic markers, including DNA repair, E2F targets, G2M checkpoint, and MYC targets V1, were enriched in Cluster2. We then constructed a prognostic risk model using three m6A-related genes that were identified as independent factors affecting OS. The nomogram based on the risk model score indicated good performance in predicting the 1-, 2-and 3-year survival of the LC patients. In conclusion, m6A-related genes are potential prognostic markers and therapeutic targets for LC.

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Section: Discussionsupporting

confidence: 84%

Section: Discussionmentioning

confidence: 99%

RNA N6-Methyladenosine-Related Gene Contribute to Clinical Prognostic Impact on Patients With Liver Cancer

et al. 2020

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“…In HCC cells, YTHDF2 can be specifically restricted by hypoxia and act as a tumor suppressor with inhibitory effect on tumor growth (67). Mechanistically, YTHDF2 directly binds m 6 A sites in 3 ′ -UTR and mediates the degradation of EGFR mRNA, which is a main upstream regulator of extracellular-signalregulated kinase/mitogen-activated protein kinase pathway.…”

Section: Ythdf2mentioning

confidence: 99%

N6-Methyladenosine: A Novel RNA Imprint in Human Cancer

Liu

et al. 2019

Front. Oncol.

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N 6 -Methyladenosine (m 6 A), a pervasive posttranscriptional modification which is reversible, has been among hotspot issues in the past several years. The balance of intracellular m 6 A levels is dynamically maintained by methyltransferase complex and demethylases. Meanwhile, m 6 A reader proteins specifically recognize modified residues and convey messages so as to set up an efficient and orderly network of m 6 A regulation. The m 6 A mark has proved to affect every step of RNA life cycle, from processing in nucleus to translation or degradation in cytoplasm. Subsequently, disorders in m 6 A methylation are directly related to aberrant RNA metabolism, which results in tumorigenesis and altered drug response. Therefore, uncovering the underlying mechanism of m 6 A in oncogenic transformation and tumor progression seeks opportunities for novel targets in cancer therapy. In this review, we conclude the extensive impact of m 6 A on RNA metabolism and highlight its relevance with human cancer, implicating the far-reaching value in clinical application.

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“…YTHDF2 directly binds the m6A modification site of EGFR 3'-UTR to promote the degradation of EGFR mRNA in HCC cells acting as a tumor suppressor to repress cancer cell proliferation and growth [114,115].…”

Section: Resultsmentioning

confidence: 99%

Analysis of eEF1Bγ interactome in the nuclear fraction of A549 human lung adenocarcinoma cells

et al. 2019

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Aim.To study the translation elongation factor eEF1B gamma (eEF1Bγ) in the nucleus of lung carcinoma cells. Methods. The protein partners of eEF1Bγin the nuclear fraction of A549 cells were identified by co-immunoprecipitation (co-IP) and liquid chromatography-tandem mass spectrometry (LC-MS/MS). The protein interaction network for nuclear eEF1Bγ was determined by Cytoscape 3.2.0 program using the MCODE plugin. Additional analysis of the eEF1Bγ partners was conducted by Map of the cell database. Results. 234 proteins interacting with eEF1Bγ in the nuclear fraction of A549 cells were identified. Possible functional networks involving these contacts were analyzed by two bioinformatic approaches. Conclusions. Splicing of pre-mRNA and regulation of mRNA stability are assumed to be the main processes in which nuclear eEF1Bγ can be involved. We hypothesize that a portion of eEF1Bγ leaves the cytoplasmlocalizede EF1B complex during carcinogenesis and enters the nucleus to regulate certain mRNAs by affecting the splicing of their pre-mRNA and/or stability of mRNA. K e y w o r d s: eEF1Bγ, protein-protein interactions, nucleus, A549 cell Structure and Function of Biopolymers

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YTHDF2 suppresses cell proliferation and growth via destabilizing the EGFR mRNA in hepatocellular carcinoma

Cited by 280 publications

References 38 publications

RNA N6-Methyladenosine-Related Gene Contribute to Clinical Prognostic Impact on Patients With Liver Cancer

RNA N6-Methyladenosine-Related Gene Contribute to Clinical Prognostic Impact on Patients With Liver Cancer

N6-Methyladenosine: A Novel RNA Imprint in Human Cancer

Analysis of eEF1Bγ interactome in the nuclear fraction of A549 human lung adenocarcinoma cells

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YTHDF2 suppresses cell proliferation and growth via destabilizing the EGFR mRNA in hepatocellular carcinoma

Cited by 280 publications

References 38 publications

RNA N6-Methyladenosine-Related Gene Contribute to Clinical Prognostic Impact on Patients With Liver Cancer

RNA N6-Methyladenosine-Related Gene Contribute to Clinical Prognostic Impact on Patients With Liver Cancer

N6-Methyladenosine: A Novel RNA Imprint in Human Cancer

Analysis of eEF1B&gamma; interactome in the nuclear fraction of A549 human lung adenocarcinoma cells

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Analysis of eEF1Bγ interactome in the nuclear fraction of A549 human lung adenocarcinoma cells