Methyltransferase‑like 1 regulates lung adenocarcinoma A549 cell proliferation and autophagy via the AKT/mTORC1 signaling pathway

Wang,Chen; Wang,Wei; Han,Xiaodan; Du,Longxia; Li,Aili; Huang,Guojin

doi:10.3892/ol.2021.12591

Methyltransferase‑like 1 regulates lung adenocarcinoma A549 cell proliferation and autophagy via the AKT/mTORC1 signaling pathway

Authors:
- Chen Wang
- Wei Wang
- Xiaodan Han
- Longxia Du
- Aili Li
- Guojin Huang
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Affiliations: Laboratory of Respiratory Diseases, The Affiliated Hospital of Guilin Medical University, Guilin, Guangxi 541001, P.R. China
Published online on: February 25, 2021 https://doi.org/10.3892/ol.2021.12591
Article Number: 330
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Methyltransferase‑like 1 (METTL1) is a transfer RNA and microRNA modifying enzyme. However, its role in lung adenocarcinoma (LUAD) remains unknown. The present study aimed to investigate the effect of METTL1 in LUAD and determine the association between METTL1 expression and prognosis of patients with LUAD. The expression profile of METTL1 in LUAD tissues was downloaded from public cancer databases and analyzed using the Gene Expression Profiling Interactive Analysis database and UALCAN online software. In addition, the association between METTL1 expression and prognosis of patients with LUAD was assessed using the Kaplan‑Meier Plotter software. The effect of METTL1 in the A549 cell line was determined in vitro via overexpression and knockdown experiments. The results demonstrated that METTL1 was upregulated in LUAD tissues, and its increased expression was associated with unfavorable prognosis. Furthermore, METTL1 promoted proliferation and colony formation of A549 cells, and inhibited autophagy via the AKT/mechanistic target of rapamycin complex 1 signaling pathway. Taken together, the results of the present study suggest that METTL1 acts as an oncogene in LUAD, thus may be a potential prognostic predictor and therapeutic target for LUAD.

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1	Herbst RS, Morgensztern D and Boshoff C: The biology and management of non-small cell lung cancer. Nature. 553:446–454. 2018. View Article : Google Scholar : PubMed/NCBI
2	Siegel RL, Miller KD and Jemal A: Cancer statistics, 2019. CA Cancer J Clin. 69:7–34. 2019. View Article : Google Scholar : PubMed/NCBI
3	Levine B and Kroemer G: Biological Functions of Autophagy Genes: A Disease Perspective. Cell. 176:11–42. 2019. View Article : Google Scholar : PubMed/NCBI
4	Levine B and Kroemer G: Autophagy in the pathogenesis of disease. Cell. 132:27–42. 2008. View Article : Google Scholar : PubMed/NCBI
5	White E: The role for autophagy in cancer. J Clin Invest. 125:42–46. 2015. View Article : Google Scholar : PubMed/NCBI
6	Barbieri I and Kouzarides T: Role of RNA modifications in cancer. Nat Rev Cancer. 20:303–322. 2020. View Article : Google Scholar : PubMed/NCBI
7	Jin S, Zhang X, Miao Y, Liang P, Zhu K, She Y, Wu Y, Liu DA, Huang J, Ren J, et al: m⁶A RNA modification controls autophagy through upregulating ULK1 protein abundance. Cell Res. 28:955–957. 2018. View Article : Google Scholar : PubMed/NCBI
8	Lin S, Liu Q, Lelyveld VS, Choe J, Szostak JW and Gregory RI: Mettl1/Wdr4-Mediated m⁷G tRNA Methylome Is Required for Normal mRNA Translation and Embryonic Stem Cell Self-Renewal and Differentiation. Mol Cell. 71:244–255.e5. 2018. View Article : Google Scholar : PubMed/NCBI
9	Pandolfini L, Barbieri I, Bannister AJ, Hendrick A, Andrews B, Webster N, Murat P, Mach P, Brandi R, Robson SC, et al: METTL1 Promotes let-7 MicroRNA Processing via m⁷G Methylation. Mol Cell. 74:1278–1290.e9. 2019. View Article : Google Scholar : PubMed/NCBI
10	Cartlidge RA, Knebel A, Peggie M, Alexandrov A, Phizicky EM and Cohen P: The tRNA methylase METTL1 is phosphorylated and inactivated by PKB and RSK in vitro and in cells. EMBO J. 24:1696–1705. 2005. View Article : Google Scholar : PubMed/NCBI
11	Okamoto M, Fujiwara M, Hori M, Okada K, Yazama F, Konishi H, Xiao Y, Qi G, Shimamoto F, Ota T, et al: tRNA modifying enzymes, NSUN2 and METTL1, determine sensitivity to 5-fluorouracil in HeLa cells. PLoS Genet. 10:e10046392014. View Article : Google Scholar : PubMed/NCBI
12	Tian QH, Zhang MF, Zeng JS, Luo RG, Wen Y, Chen J, Gan LG and Xiong JP: METTL1 overexpression is correlated with poor prognosis and promotes hepatocellular carcinoma via PTEN. J Mol Med (Berl). 97:1535–1545. 2019. View Article : Google Scholar : PubMed/NCBI
13	Wang Q, Li A, Jin J and Huang G: Targeted interfering DEP domain containing 1 protein induces apoptosis in A549 lung adenocarcinoma cells through the NF-κB signaling pathway. Onco Targets Ther. 10:4443–4454. 2017. View Article : Google Scholar : PubMed/NCBI
14	Klionsky DJ, Abdelmohsen K, Abe A, Abedin MJ, Abeliovich H, Acevedo Arozena A, Adachi H, Adams CM, Adams PD, Adeli K, et al: Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). Autophagy. 12:1–222. 2016. View Article : Google Scholar : PubMed/NCBI
15	Li A, Wang Q, He G, Jin J and Huang G: DEP domain containing 1 suppresses apoptosis via inhibition of A20 expression, which activates the nuclear factor κB signaling pathway in HepG2 cells. Oncol Lett. 16:949–955. 2018.PubMed/NCBI
16	Landi MT, Dracheva T, Rotunno M, Figueroa JD, Liu H, Dasgupta A, Mann FE, Fukuoka J, Hames M, Bergen AW, et al: Gene expression signature of cigarette smoking and its role in lung adenocarcinoma development and survival. PLoS One. 3:e16512008. View Article : Google Scholar : PubMed/NCBI
17	Huang W, Sherman BT and Lempicki RA: Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc. 4:44–57. 2009. View Article : Google Scholar : PubMed/NCBI
18	Amin MB, Greene FL, Edge SB, Compton CC, Gershenwald JE, Brookland RK, Meyer L, Gress DM, Byrd DR and Winchester DP: The Eighth Edition AJCC Cancer Staging Manual: Continuing to build a bridge from a population-based to a more ‘personalized’ approach to cancer staging. CA Cancer J Clin. 67:93–99. 2017. View Article : Google Scholar : PubMed/NCBI
19	Liu Y, Zhang Y, Chi Q, Wang Z and Sun B: Methyltransferase-like 1 (METTL1) served as a tumor suppressor in colon cancer by activating 7-methyguanosine (m⁷G) regulated let-7e miRNA/HMGA2 axis. Life Sci. 249:1174802020. View Article : Google Scholar : PubMed/NCBI
20	Marinković M, Šprung M, Buljubašić M and Novak I: Autophagy Modulation in cancer: current knowledge on action and therapy. Oxid Med Cell Longev. 2018:80238212018. View Article : Google Scholar : PubMed/NCBI
21	Manning BD and Toker A: AKT/PKB Signaling: Navigating the Network. Cell. 169:381–405. 2017. View Article : Google Scholar : PubMed/NCBI
22	Saxton RA and Sabatini DM: mTOR Signaling in Growth, Metabolism, and Disease. Cell 168: 960–976, 2017. Erratum in: Cell. 169:361–371. 2017.