Role of m6A modification in regulating the PI3K/AKT signaling pathway in cancer

Liu, Jie; Gu, Xinyu; Guan, Zhenjie; Huang, Di; Xing, Huiwu; Zheng, Lian

doi:10.1186/s12967-023-04651-0

Cited by 3 publications

(2 citation statements)

References 217 publications

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“…The PI3K signaling pathway can undergo aberrant activation through several mechanisms: activating mutations or amplification of PI3K catalytic subunits, inactivation of the lipid phosphatase PTEN (phosphatase and tensin homolog), or amplification or mutation of cellular receptors. Notably, PTEN serves as a critical negative regulator within this pathway, countering the actions of PI3K/AKT signaling (25). Discovered in the 1970s, protein kinase AKT, also known as protein kinase B, was identified as an oncogene by the transforming retrovirus AKT-8, which was isolated from the AKR mouse thymoma cell line.…”

Section: Immune Microenvironment In Gi Cancersmentioning

confidence: 99%

Pathways and molecules for overcoming immunotolerance in metastatic gastrointestinal tumors

Gan,

Li,

et al. 2024

Front. Immunol.

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Worldwide, gastrointestinal (GI) cancer is recognized as one of the leading malignancies diagnosed in both genders, with mortality largely attributed to metastatic dissemination. It has been identified that in GI cancer, a variety of signaling pathways and key molecules are modified, leading to the emergence of an immunotolerance phenotype. Such modifications are pivotal in the malignancy’s evasion of immune detection. Thus, a thorough analysis of the pathways and molecules contributing to GI cancer’s immunotolerance is vital for advancing our comprehension and propelling the creation of efficacious pharmacological treatments. In response to this necessity, our review illuminates a selection of groundbreaking cellular signaling pathways associated with immunotolerance in GI cancer, including the Phosphoinositide 3-kinases/Akt, Janus kinase/Signal Transducer and Activator of Transcription 3, Nuclear Factor kappa-light-chain-enhancer of activated B cells, Transforming Growth Factor-beta/Smad, Notch, Programmed Death-1/Programmed Death-Ligand 1, and Wingless and INT-1/beta-catenin-Interleukin 10. Additionally, we examine an array of pertinent molecules like Indoleamine-pyrrole 2,3-dioxygenase, Human Leukocyte Antigen G/E, Glycoprotein A Repetitions Predominant, Clever-1, Interferon regulatory factor 8/Osteopontin, T-cell immunoglobulin and mucin-domain containing-3, Carcinoembryonic antigen-related cell adhesion molecule 1, Cell division control protein 42 homolog, and caspases-1 and -12.

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Section: Immune Microenvironment In Gi Cancersmentioning

confidence: 99%

Pathways and molecules for overcoming immunotolerance in metastatic gastrointestinal tumors

Gan,

Li,

et al. 2024

Front. Immunol.

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“…The phosphoinositide 3 kinase (PI3K) pathway has been linked closely with kidney cancer, characterized by hyperactivation of PI3K and AKT signaling ( 15 ). Various types of cancer, including renal cancer, show a connection between altered PI3K/AKT pathway activation and changes in m6A mRNA methylation or its regulators ( 16 ). In renal cancer cells, overexpression of METTL3 leads to decreased PI3K/AKT activation as well as suppressed tumor growth ( 17 ), suggesting a PI3K/Akt-dependent regulatory function of m6A modification in ccRCC.…”

Section: Introductionmentioning

confidence: 99%

Von Hippel Lindau tumor suppressor controls m6A-dependent gene expression in renal tumorigenesis

Zhang,

Yu,

Hepperla

et al. 2024

Journal of Clinical Investigation

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N6-Methyladenosine (m6A) is the most abundant posttranscriptional modification, and its contribution to cancer evolution has recently been appreciated. Renal cancer is the most common adult genitourinary cancer, approximately 85% of which is accounted for by the clear cell renal cell carcinoma (ccRCC) subtype characterized by VHL loss. However, it is unclear whether VHL loss in ccRCC affects m6A patterns. In this study, we demonstrate that VHL binds and promotes METTL3/METTL14 complex formation while VHL depletion suppresses m6A modification, which is distinctive from its canonical E3 ligase role. m6A RNA immunoprecipitation sequencing (RIP-Seq) coupled with RNA-Seq allows us to identify a selection of genes whose expression may be regulated by VHL-m6A signaling. Specifically, PIK3R3 is identified to be a critical gene whose mRNA stability is regulated by VHL in a m6A-dependent but HIF-independent manner. Functionally, PIK3R3 depletion promotes renal cancer cell growth and orthotopic tumor growth while its overexpression leads to decreased tumorigenesis. Mechanistically, the VHL-m6A–regulated PIK3R3 suppresses tumor growth by restraining PI3K/AKT activity. Taken together, we propose a mechanism by which VHL regulates m6A through modulation of METTL3/METTL14 complex formation, thereby promoting PIK3R3 mRNA stability and protein levels that are critical for regulating ccRCC tumorigenesis.

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The combination of methionine adenosyltransferase 2A inhibitor and methyltransferase like 3 inhibitor promotes apoptosis of non-small cell lung cancer cells and produces synergistic anti-tumor activity

Xuan,

Lu,

et al. 2024

Biochemical and Biophysical Research Communications

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Role of m6A modification in regulating the PI3K/AKT signaling pathway in cancer

Cited by 3 publications

References 217 publications

Pathways and molecules for overcoming immunotolerance in metastatic gastrointestinal tumors

Pathways and molecules for overcoming immunotolerance in metastatic gastrointestinal tumors

Von Hippel Lindau tumor suppressor controls m6A-dependent gene expression in renal tumorigenesis

The combination of methionine adenosyltransferase 2A inhibitor and methyltransferase like 3 inhibitor promotes apoptosis of non-small cell lung cancer cells and produces synergistic anti-tumor activity

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