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

Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71(3):209–49.

Article  PubMed  Google Scholar 

Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, Yu XQ, He J. Cancer statistics in China, 2015. CA Cancer J Clin. 2016;66(2):115–32.

Article  PubMed  Google Scholar 

Huang KK, Ramnarayanan K, Zhu F, Srivastava S, Xu C, Tan ALK, Lee M, Tay S, Das K, Xing M, et al. Genomic and epigenomic profiling of high-risk intestinal metaplasia reveals molecular determinants of progression to gastric cancer. Cancer Cell. 2018;33(1):137.

Article  CAS  PubMed  Google Scholar 

Wang K, Yuen ST, Xu J, Lee SP, Yan HHN, Shi ST, Siu HC, Deng S, Chu KM, Law S, et al. Whole-genome sequencing and comprehensive molecular profiling identify new driver mutations in gastric cancer. Nat Genet. 2014;46(6):573–82.

Article  CAS  PubMed  Google Scholar 

Jia G, Fu Y, Zhao X, Dai Q, Zheng G, Yang Y, Yi C, Lindahl T, Pan T, Yang Y-G, et al. N6-methyladenosine in nuclear RNA is a major substrate of the obesity-associated FTO. Nat Chem Biol. 2011;7(12):885–7.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Deng X, Su R, Weng H, Huang H, Li Z, Chen J. RNA N-methyladenosine modification in cancers: current status and perspectives. Cell Res. 2018;28(5):507–17.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Meyer KD, Jaffrey SR. Rethinking mA Readers, Writers, and Erasers. Annu Rev Cell Dev Biol. 2017;33:319–42.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wang X, Zhao BS, Roundtree IA, Lu Z, Han D, Ma H, Weng X, Chen K, Shi H, He C. N(6)-methyladenosine modulates messenger RNA translation efficiency. Cell. 2015;161(6):1388–99.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Du H, Zhao Y, He J, Zhang Y, Xi H, Liu M, Ma J, Wu L. YTHDF2 destabilizes m(6)A-containing RNA through direct recruitment of the CCR4-NOT deadenylase complex. Nat Commun. 2016;7:12626.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Li Y, Sheng H, Ma F, Wu Q, Huang J, Chen Q, Sheng L, Zhu X, Zhu X, Xu M. RNA mA reader YTHDF2 facilitates lung adenocarcinoma cell proliferation and metastasis by targeting the AXIN1/Wnt/β-catenin signaling. Cell Death Dis. 2021;12(5):479.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zhao T, Wang M, Zhao X, Weng S, Qian K, Shi K, Gu Y, Ying W, Qian X, Zhang Y. YTHDF2 Inhibits the migration and invasion of lung adenocarcinoma by negatively regulating the FAM83D-TGFβ1-SMAD2/3 pathway. Front Oncol. 2022;12:763341.

Article  PubMed  PubMed Central  Google Scholar 

Zhong L, Liao D, Zhang M, Zeng C, Li X, Zhang R, Ma H, Kang T. YTHDF2 suppresses cell proliferation and growth via destabilizing the EGFR mRNA in hepatocellular carcinoma. Cancer Lett. 2019;442:252–61.

Article  CAS  PubMed  Google Scholar 

Hou J, Zhang H, Liu J, Zhao Z, Wang J, Lu Z, Hu B, Zhou J, Zhao Z, Feng M, et al. YTHDF2 reduction fuels inflammation and vascular abnormalization in hepatocellular carcinoma. Mol Cancer. 2019;18(1):163.

Article  PubMed  PubMed Central  Google Scholar 

Sheng H, Li Z, Su S, Sun W, Zhang X, Li L, Li J, Liu S, Lu B, Zhang S, et al. YTH domain family 2 promotes lung cancer cell growth by facilitating 6-phosphogluconate dehydrogenase mRNA translation. Carcinogenesis. 2020;41(5):541–50.

Article  CAS  PubMed  Google Scholar 

Yang C-L, Qiu X, Lin J-Y, Chen X-Y, Zhang Y-M, Hu X-Y, Zhong J-H, Tang S, Li X-Y, Xiang B-D, et al. Potential role and clinical value of PPP2CA in hepatocellular carcinoma. J Clin Transl Hepatol. 2021;9(5):661–71.

PubMed  PubMed Central  Google Scholar 

Arriazu E, Pippa R, Odero MD. Protein phosphatase 2A as a therapeutic target in acute myeloid leukemia. Front Oncol. 2016;6:78.

Article  PubMed  PubMed Central  Google Scholar 

Zhang C, Kang T, Wang X, Wang J, Liu L, Zhang J, Liu X, Li R, Wang J, Zhang J. LINC-PINT suppresses cisplatin resistance in gastric cancer by inhibiting autophagy activation epigenetic silencing of ATG5 by EZH2. Front Pharmacol. 2022;13:968223.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Dixit D, Prager BC, Gimple RC, Poh HX, Wang Y, Wu Q, Qiu Z, Kidwell RL, Kim LJY, Xie Q, et al. The RNA m6A reader YTHDF2 maintains oncogene expression and is a targetable dependency in glioblastoma stem cells. Cancer Discov. 2021;11(2):480–99.

Article  CAS  PubMed  Google Scholar 

Hou G, Zhao X, Li L, Yang Q, Liu X, Huang C, Lu R, Chen R, Wang Y, Jiang B, et al. SUMOylation of YTHDF2 promotes mRNA degradation and cancer progression by increasing its binding affinity with m6A-modified mRNAs. Nucleic Acids Res. 2021;49(5):2859–77.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Paris J, Morgan M, Campos J, Spencer GJ, Shmakova A, Ivanova I, Mapperley C, Lawson H, Wotherspoon DA, Sepulveda C, et al. Targeting the RNA mA reader YTHDF2 selectively compromises cancer stem cells in acute myeloid leukemia. Cell Stem Cell. 2019;25(1):137.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Su R, Dong L, Li C, Nachtergaele S, Wunderlich M, Qing Y, Deng X, Wang Y, Weng X, Hu C, et al. R-2HG exhibits anti-tumor activity by targeting FTO/mA/MYC/CEBPA signaling. Cell. 2018;172(1–2):90.

Article  CAS  PubMed  Google Scholar 

Yang S, Wei J, Cui Y-H, Park G, Shah P, Deng Y, Aplin AE, Lu Z, Hwang S, He C, et al. m6A mRNA demethylase FTO regulates melanoma tumorigenicity and response to anti-PD-1 blockade. Nat Commun. 2019;10(1):2782.

Article  PubMed  PubMed Central  Google Scholar 

Yan J, Huang X, Zhang X, Chen Z, Ye C, Xiang W, Huang Z. LncRNA LINC00470 promotes the degradation of PTEN mRNA to facilitate malignant behavior in gastric cancer cells. Biochem Biophys Res Commun. 2020;521(4):887–93.

Article  CAS  PubMed  Google Scholar 

Shen X, Zhao K, Xu L, Cheng G, Zhu J, Gan L, Wu Y, Zhuang Z. YTHDF2 inhibits gastric cancer cell growth by regulating FOXC2 signaling pathway. Front Genet. 2020;11:592042.

Article  CAS  PubMed  Google Scholar 

Jin D, Guo J, Wu Y, Yang L, Wang X, Du J, Dai J, Chen W, Gong K, Miao S, et al. mA demethylase ALKBH5 inhibits tumor growth and metastasis by reducing YTHDFs-mediated YAP expression and inhibiting miR-107/LATS2-mediated YAP activity in NSCLC. Mol Cancer. 2020;19(1):40.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Crispín JC, Hedrich CM, Tsokos GC. Gene-function studies in systemic lupus erythematosus. Nat Rev Rheumatol. 2013;9(8):476–84.

Article  PubMed  Google Scholar 

Kiely M, Kiely PA. PP2A: The Wolf in Sheep’s Clothing? Cancers (Basel). 2015;7(2):648–69.

Article  CAS  PubMed  Google Scholar 

Shi Y. Serine/threonine phosphatases: mechanism through structure. Cell. 2009;139(3):468–84.

Article  CAS  PubMed  Google Scholar 

Fowle H, Zhao Z, Graña X. PP2A holoenzymes, substrate specificity driving cellular functions and deregulation in cancer. Adv Cancer Res. 2019;144:55–93.

Article  PubMed  Google Scholar 

Westermarck J, Hahn WC. Multiple pathways regulated by the tumor suppressor PP2A in transformation. Trends Mol Med. 2008;14(4):152–60.

Article  CAS  PubMed  Google Scholar 

Zimmerman R, Peng DJ, Lanz H, Zhang YH, Danen-Van Oorschot A, Qu S, Backendorf C, Noteborn M. PP2A inactivation is a crucial step in triggering apoptin-induced tumor-selective cell killing. Cell Death Dis. 2012;3:e291.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Cheng Z, Gao S, Liang X, Lian C, Chen J, Fang C. Inhibiting PP2Ac promotes the malignant phenotype of gastric cancer cells through the ATM/METTL3 Axis. Biomed Res Int. 2021;2021:1015293.

Article  PubMed  PubMed Central  Google Scholar 

O’Connor CM, Perl A, Leonard D, Sangodkar J, Narla G. Therapeutic targeting of PP2A. Int J Biochem Cell Biol. 2018;96:182–93.

Article  PubMed  Google Scholar 

Perrotti D, Neviani P. Protein phosphatase 2A: a target for anticancer therapy. Lancet Oncol. 2013;14(6):e229–38.

Article  CAS  PubMed  PubMed Central 

留言 (0)

沒有登入
gif