Inhibiting PP2Acα Promotes the Malignant Phenotype of Gastric Cancer Cells through the ATM/METTL3 Axis

Cheng, Zhaoxiang; Gao, Shan; Liang, Xiaojie; Lian, Chao; Chen, Jianquan; Fang, Chao

doi:10.1155/2021/1015293

Cited by 4 publications

(1 citation statement)

References 43 publications

(49 reference statements)

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“…PP2A, as a confirmed tumor suppressor, was verified to be altered or functionally inactivated in many tumors [ 30 , 31 ]. So far, the basic research about stomach cancer has not involved PP2Acα/PPP2CA except that PP2Acα plays an antineoplastic role through the ATM/METTL3 Axis in Cheng’s research [ 32 ]. In our work, we identified PPP2CA as a direct downstream of YTHDF2 by combining a comprehensive analysis of bioinformatics strategies and experimental evidence.…”

Section: Discussionmentioning

confidence: 99%

YTHDF2 exerts tumor-suppressor roles in gastric cancer via up-regulating PPP2CA independently of m6A modification

Zhou

Fan²,

Dou³

et al. 2023

Biol Proced Online

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Background YTHDF2 is one of important readers of N6-methyladenosine (m6A) modification on RNA. Growing evidence implicates that YTHDF2 takes an indispensable part in the regulation of tumorigenesis and metastasis in different cancers, but its biological functions and underlying mechanisms remain elusive in gastric cancer (GC). Aim To investigate the clinical relevance and biological function of YTHDF2 in GC. Results Compared with matched normal stomach tissues, YTHDF2 expression was markedly decreased in gastric cancer tissues. The expression level of YTHDF2 was inversely associated with gastric cancer patients’ tumor size, AJCC classification and prognosis. Functionally, YTHDF2 reduction facilitated gastric cancer cell growth and migration in vitro and in vivo, whereas YTHDF2 overexpression exhibited opposite phenotypes. Mechanistically, YTHDF2 enhanced expression of PPP2CA, the catalytic subunit of PP2A (Protein phosphatase 2A), in an m6A-independent manner, and silencing of PPP2CA antagonized the anti-tumor effects caused by overexpression of YTHDF2 in GC cells. Conclusion These findings demonstrate that YTHDF2 is down-regulated in GC and its down-regulation promotes GC progression via a possible mechanism involving PPP2CA expression, suggesting that YTHDF2 may be a hopeful biomarker for diagnosis and an unrevealed treatment target for GC.

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Section: Discussionmentioning

confidence: 99%

YTHDF2 exerts tumor-suppressor roles in gastric cancer via up-regulating PPP2CA independently of m6A modification

Zhou

Fan²,

Dou³

et al. 2023

Biol Proced Online

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show abstract

miRNA/epithelial-mesenchymal axis (EMT) axis as a key player in cancer progression and metastasis: A focus on gastric and bladder cancers

Sahib,

Fawzi,

Zabibah

et al. 2023

Cellular Signalling

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New insights into the regulation of METTL3 and its role in tumors

Jin,

Qu,

Quan

2023

Cell Commun Signal

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As one of the most abundant epigenetic modifications in RNA, N6-methyladenosine (m6A) affects RNA transcription, splicing, stability, and posttranscriptional translation. Methyltransferase-like 3 (METTL3), a key component of the m6A methyltransferase complex, dynamically regulates target genes expression through m6A modification. METTL3 has been found to play a critical role in tumorigenesis, tumor growth, metastasis, metabolic reprogramming, immune cell infiltration, and tumor drug resistance. As a result, the development of targeted drugs against METTL3 is becoming increasingly popular. This review systematically summarizes the factors that regulate METTL3 expression and explores the specific mechanisms by which METTL3 affects multiple tumor biological behaviors. We aim to provide fundamental support for tumor diagnosis and treatment, at the same time, to offer new ideas for the development of tumor-targeting drugs.

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Inhibiting PP2Acα Promotes the Malignant Phenotype of Gastric Cancer Cells through the ATM/METTL3 Axis

Cited by 4 publications

References 43 publications

YTHDF2 exerts tumor-suppressor roles in gastric cancer via up-regulating PPP2CA independently of m6A modification

YTHDF2 exerts tumor-suppressor roles in gastric cancer via up-regulating PPP2CA independently of m6A modification

miRNA/epithelial-mesenchymal axis (EMT) axis as a key player in cancer progression and metastasis: A focus on gastric and bladder cancers

New insights into the regulation of METTL3 and its role in tumors

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