Fat mass and obesity‐associated protein regulates tumorigenesis of arecoline‐promoted human oral carcinoma

Li, Xia; Xie, Xiaoli; Gu, Yangcong; Zhang, Jianming; Jin, Song; Cheng, Xiufeng; Gao, Yijun; Ai, Yilong

doi:10.1002/cam4.4188

Cited by 24 publications

(40 citation statements)

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“…Our previous study demonstrated that chronic low‐dose arecoline‐treated OSCC cell lines (hereinafter referred to as CAL27‐A and SCC25‐A) exhibit superior tumorigenic effects to original OSCC cell lines (CAL27 and SCC25), and FTO plays a vital role in chronic arecoline‐exposure‐promoted oncogenicity of OSCC cells. 21 To elucidate the potential molecular mechanism underlying arecoline‐promoted oral cancer malignance, we conducted an RNA‐seq transcriptome assay using CAL27‐A and CAL27 cells. A total of 188 genes and 370 genes were significantly ( P < 0.05 and fold change >2 or <0.5) upregulated and downregulated in arecoline‐treated CAL27 (CAL27‐A) compared to CAL27, respectively (Figure 1A ).…”

Section: Resultsmentioning

confidence: 99%

“…Several FTO inhibitors, such as R-2-hydroxyglutarate (R-2HG), FB23, and FB23-2, exert potent anti-leukemic activity both in vitro and in vivo. 19,20 In a previous study, we described how FTO upregulation is pivotal for arecoline-treated OSCC acquiring malignant phenotypes, 21 but the underlying molecular mechanism is unknown. In the current study, we aim to identify the critical mRNA target of FTO and to explore a potential targeted therapy to treat arecoline-induced OSCC.…”

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confidence: 99%

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Fat mass and obesity‐associated protein regulates arecoline‐exposed oral cancer immune response through programmed cell death‐ligand 1

Chen

Gao

et al. 2022

Cancer Science

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The high prevalence of oral squamous cell carcinoma (OSCC) in South Asia is associated with habitual areca nut chewing. Arecoline, a primary active carcinogen within areca nut extract, is known to promote OSCC pathological development. Dysregulation of N6‐methyladenosine (m6A) modification has begun to emerge as a significant contributor to cancer development and progression. However, the biological effects and molecular mechanisms of m6A modification in arecoline‐promoted OSCC malignance remain elusive. We reveal that chronic arecoline exposure substantially induces upregulation of fat mass and obesity‐associated protein (FTO), MYC, and programmed cell death‐ligand 1 (PD‐L1) in OSCC cells. Moreover, upregulation of PD‐L1 is observed in OSCC cell lines and tissues and is associated with areca nut chewing in OSCC patients. We also demonstrate that arecoline‐induced FTO promotes the stability and expression levels of PD ‐ L1 transcripts through mediating m6A modification and MYC activity, respectively. PD‐L1 upregulation confers superior cell proliferation, migration, and resistance to T‐cell killing to OSCC cells. Blockage of PD‐L1 by administration of anti‐PD‐L1 antibody shrinks tumor size and improves mouse survival by elevating T‐cell‐mediated tumor cell killing. Therefore, targeting PD‐L1 might be a potential therapeutic strategy for treating PD‐L1‐positive OSCC patients, especially those with habitual areca nut chewing.

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Section: Resultsmentioning

confidence: 99%

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confidence: 99%

Fat mass and obesity‐associated protein regulates arecoline‐exposed oral cancer immune response through programmed cell death‐ligand 1

Chen

Gao

et al. 2022

Cancer Science

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“…First, it oxidizes m 6 A to N6-hydroxymethyl adenosine (Hm 6 A), then converts Hm 6 A to N6-formyl adenosine (F 6 A) and ultimately converts F 6 A to adenosine to finalize the m 6 A demethylation process (16). Studies have indicated that FTO is involved in autophagy, cell proliferation and chemotherapy resistance (59)(60)(61). Furthermore, ALKBH5 has been closely associated with chemotherapy resistance (62).…”

Section: Rna Modification and M 6 Amentioning

confidence: 99%

Roles of m⁶A modification in oral cancer (Review)

et al. 2022

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Oral cancer is one of the highly malignant tumors with poor prognosis. The pathogenic mechanisms of oral cancer have remained to be fully elucidated and this brings significant challenges to the treatment. RNA modification is a common intracellular chemical modification that has been related to various pathological processes, such as blood diseases, immune system diseases and cancer. As the most common and abundant RNA modification in eukaryotic mRNA, N 6 -methyladenosine (m 6 A) modification has a crucial role in several cancers, including oral cancer. m 6 A modification directly affects gene expression levels and regulates various physiological and pathological processes. It has been demonstrated that m 6 A modification may affect the proliferation, migration and invasion of oral cancer cells by regulating the level of m 6 A modification. In the present review, the effects of m 6 A modification on the proliferation and death of oral cancer cells, as well as the occurrence and development of oral cancer, were analyzed in order to provide a new target for treatment. Furthermore, the roles of m 6 A modification in chemotherapy resistance and potential immunotherapy were analyzed and new treatment ideas were provided.

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“…Furthermore, FTO upregulation in oral squamous cell carcinoma causes further tumor progression, whereas FTO downregulation remarkably represses tumor cell proliferation, colony formation and tumor growth (Li et al, 2021a). The in vivo assays in mice indicated that FTO knockdown slows down tumor growth (Li et al, 2021b). Subsequently, FTO might act as an effective therapeutic target against OSCC.…”

Section: Oral Squamous Cell Carcinomamentioning

confidence: 99%

Effect of demethyltransferase FTO on tumor progression

SHENG¹,

Shen²,

Yang³

2022

Biocell

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N 6 -methyladenosine (m 6 A) modification is the most widespread and conserved internal mRNA modification in mammalian cells. It greatly affects genetic regulation by enhancing the involvement of diverse cellular enzymes and thus, plays a significant role in basic life processes. Numerous studies on m 6 A modification identified FTO as a crucial demethylase that participates in various biological processes. Not only does FTO play a pivotal role in obesity-related conditions, but it also influences the occurrence, development, and prognosis of several cancers, such as acute myeloid leukemia, breast cancer, liver cancer, and lung cancer. Moreover, FTO also shows a close association with immunity and viral infections. This article summarized the molecular mechanism of FTO in tumorigenesis and tumor progression.

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Fat mass and obesity‐associated protein regulates tumorigenesis of arecoline‐promoted human oral carcinoma

Abstract: This is an open access article under the terms of the Creat ive Commo ns Attri bution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 24 publications

References 32 publications

Fat mass and obesity‐associated protein regulates arecoline‐exposed oral cancer immune response through programmed cell death‐ligand 1

Fat mass and obesity‐associated protein regulates arecoline‐exposed oral cancer immune response through programmed cell death‐ligand 1

Roles of m⁶A modification in oral cancer (Review)

Effect of demethyltransferase FTO on tumor progression

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Fat mass and obesity‐associated protein regulates tumorigenesis of arecoline‐promoted human oral carcinoma

Abstract: This is an open access article under the terms of the Creat ive Commo ns Attri bution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 24 publications

References 32 publications

Fat mass and obesity‐associated protein regulates arecoline‐exposed oral cancer immune response through programmed cell death‐ligand 1

Fat mass and obesity‐associated protein regulates arecoline‐exposed oral cancer immune response through programmed cell death‐ligand 1

Roles of m6A modification in oral cancer (Review)

Effect of demethyltransferase FTO on tumor progression

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Roles of m⁶A modification in oral cancer (Review)