ATIC facilitates cell growth and migration by upregulating Myc expression in lung adenocarcinoma

Niu,Niu; Zeng,Jialong; Ke,Xianni; Zheng,Wenyu; Fu,Chunmei; Lv,Shiqi; Fu,Jianghong; Yu,Yang

doi:10.3892/ol.2022.13251

ATIC facilitates cell growth and migration by upregulating Myc expression in lung adenocarcinoma

Authors:
- Niu Niu
- Jialong Zeng
- Xianni Ke
- Wenyu Zheng
- Chunmei Fu
- Shiqi Lv
- Jianghong Fu
- Yang Yu
View Affiliations

Affiliations: Department of Internal Medicine, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital and Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, Guangdong 518116, P.R. China, Department of Internal Medicine, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital and Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, Guangdong 518116, P.R. China
Published online on: February 23, 2022 https://doi.org/10.3892/ol.2022.13251
Article Number: 131
Copyright: © Niu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

5‑Aminoimidazole‑4‑carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase (ATIC), a catalysing enzyme in the de novo purine biosynthetic pathway, has been previously reported to be upregulated and to participate in myeloma and hepatocellular carcinoma progression. In the present study, by using bioinformatics technology, a higher ATIC expression was identified in lung adenocarcinoma (LUAD) tissues than in normal tissues, and ATIC expression was found to be positively associated with Myc expression in LUAD tissues. In addition, the role of ATIC in modulating the growth and migration of LUAD cells was explored and the involvement of Myc was revealed. ATIC expression in 56 paired LUAD and tumour adjacent non‑cancerous tissues was assessed using reverse transcription‑quantitative PCR and western blot analysis. Pearson's correlation analysis was applied to evaluate the correlation between ATIC and Myc expression levels in LUAD tissues. A rescue experiment was performed to explore the role of ATIC/Myc in regulating the growth, migration and invasion of HCC827 and NCI‑H1435 cells. It was demonstrated that ATIC was overexpressed in LUAD tissues, particularly in advanced‑stage LUAD, and was predicted to be associated with an advanced TNM stage, a higher lymph node metastasis rate, poor tissue differentiation and a lower overall survival rate. ATIC overexpression promoted cell growth, migratory and invasive capacities, whereas this effect was abrogated by Myc knockdown in the HCC827 and NCI‑H1435 cells. On the whole, the present study demonstrates that ATIC promotes LUAD cell growth and migration by increasing Myc expression.

View Figures

View References

1	Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A and Bray F: Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 71:209–249. 2021. View Article : Google Scholar : PubMed/NCBI
2	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
3	Xu Y, Jiang Q, Liu H, Xiao X, Yang D, Saw PE and Luo B: DHX37 impacts prognosis of hepatocellular carcinoma and lung adenocarcinoma through immune infiltration. J Immunol Res. 2020:88353932020. View Article : Google Scholar : PubMed/NCBI
4	Xu Y, Liu Z, Li H, Feng S, Li Q, Li J and Li S: VEGI downregulation is correlated with nodal metastasis and poor prognosis in lung adenocarcinoma. Mol Clin Oncol. 14:252021. View Article : Google Scholar : PubMed/NCBI
5	Cai J, Deng H, Luo L, You L, Liao H and Zheng Y: Decreased expression of JAK1 associated with immune infiltration and poor prognosis in lung adenocarcinoma. Aging (Albany NY). 13:2073–2088. 2020. View Article : Google Scholar : PubMed/NCBI
6	Robinson AD, Eich ML and Varambally S: Dysregulation of de novo nucleotide biosynthetic pathway enzymes in cancer and targeting opportunities. Cancer Lett. 470:134–140. 2020. View Article : Google Scholar : PubMed/NCBI
7	Lv Y, Wang X, Li X, Xu G, Bai Y, Wu J, Piao Y, Shi Y, Xiang R and Wang L: Nucleotide de novo synthesis increases breast cancer stemness and metastasis via cGMP-PKG-MAPK signaling pathway. PLoS Biol. 18:e30008722020. View Article : Google Scholar : PubMed/NCBI
8	Fan TWM, Bruntz RC, Yang Y, Song H, Chernyavskaya Y, Deng P, Zhang Y, Shah PP, Beverly LJ, Qi Z, et al: De novo synthesis of serine and glycine fuels purine nucleotide biosynthesis in human lung cancer tissues. J Biol Chem. 294:13464–13477. 2019. View Article : Google Scholar : PubMed/NCBI
9	Yamaoka T, Kondo M, Honda S, Iwahana H, Moritani M, Ii S, Yoshimoto K and Itakura M: Amidophosphoribosyltransferase limits the rate of cell growth-linked de novo purine biosynthesis in the presence of constant capacity of salvage purine biosynthesis. J Biol Chem. 272:17719–17725. 1997. View Article : Google Scholar : PubMed/NCBI
10	Verma P, Kar B, Varshney R, Roy P and Sharma AK: Characterization of AICAR transformylase/IMP cyclohydrolase (ATIC) from Staphylococcus lugdunensis. FEBS J. 284:4233–4261. 2017. View Article : Google Scholar : PubMed/NCBI
11	Li R, Chen G, Dang Y, He R, Liu A, Ma J and Wang C: Upregulation of ATIC in multiple myeloma tissues based on tissue microarray and gene microarrays. Int J Lab Hematol. 43:409–417. 2021. View Article : Google Scholar : PubMed/NCBI
12	Li M, Jin C, Xu M, Zhou L, Li D and Yin Y: Bifunctional enzyme ATIC promotes propagation of hepatocellular carcinoma by regulating AMPK-mTOR-S6 K1 signaling. Cell communication and signaling. Cell Commun Signal. 15:522017. View Article : Google Scholar : PubMed/NCBI
13	Hsieh AL, Walton ZE, Altman BJ, Stine ZE and Dang CV: MYC and metabolism on the path to cancer. Semin Cell Dev Biol. 43:11–21. 2015. View Article : Google Scholar : PubMed/NCBI
14	Dang CV: MYC on the path to cancer. Cell. 149:22–35. 2012. View Article : Google Scholar : PubMed/NCBI
15	Ma L, Young J, Prabhala H, Pan E, Mestdagh P, Muth D, Teruya-Feldstein J, Reinhardt F, Onder TT, Valastyan S, et al: miR-9, a MYC/MYCN-activated microRNA, regulates E-cadherin and cancer metastasis. Nat Cell Biol. 12:247–256. 2010. View Article : Google Scholar : PubMed/NCBI
16	Zack TI, Schumacher SE, Carter SL, Cherniack AD, Saksena G, Tabak B, Lawrence MS, Zhsng CZ, Wala J, Mermel CH, et al: Pan-cancer patterns of somatic copy number alteration. Nat Genet. 45:1134–1140. 2013. View Article : Google Scholar : PubMed/NCBI
17	Shen P, Reineke LC, Knutsen E, Chen M, Pichler M, Ling H and Calin GA: Metformin blocks MYC protein synthesis in colorectal cancer via mTOR-4EBP-eIF4E and MNK1-eIF4G-eIF4E signaling. Mol Oncol. 12:1856–1870. 2018. View Article : Google Scholar : PubMed/NCBI
18	Xu D, Xie R, Xu Z, Zhao Z, Ding M, Chen W, Zhang J, Mao E, Chen E, Chen Y, et al: mTOR-Myc axis drives acinar-to-dendritic cell transition and the CD4⁺ T cell immune response in acute pancreatitis. Cell Death Dis. 11:4162020. View Article : Google Scholar : PubMed/NCBI
19	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
20	Greasley SE, Horton P, Ramcharan J, Beardsley GP, Benkovic SJ and Wilson IA: Crystal structure of a bifunctional transformylase and cyclohydrolase enzyme in purine biosynthesis. Nat Struct Biol. 8:402–406. 2001. View Article : Google Scholar : PubMed/NCBI
21	Vergis JM, Bulock KG, Fleming KG and Beardsley GP: Human 5-aminoimidazole-4-carboxamide ribonucleotide transformylase/inosine 5′-monophosphate cyclohydrolase. A bifunctional protein requiring dimerization for transformylase activity but not for cyclohydrolase activity. J Biol Chem. 276:7727–7733. 2001. View Article : Google Scholar : PubMed/NCBI
22	Racanelli AC, Rothbart SB, Heyer CL and Moran RG: Therapeutics by cytotoxic metabolite accumulation: Pemetrexed causes ZMP accumulation, AMPK activation, and mammalian target of rapamycin inhibition. Cancer Res. 69:5467–5474. 2009. View Article : Google Scholar : PubMed/NCBI
23	Park JA and Shin HY: ATIC gene polymorphism and histologic response to chemotherapy in pediatric osteosarcoma. J Pediatr Hematol Oncol. 39:e270–e274. 2017. View Article : Google Scholar : PubMed/NCBI
24	Zhu J, Wang M and Hu D: Development of an autophagy-related gene prognostic signature in lung adenocarcinoma and lung squamous cell carcinoma. PeerJ. 8:e82882020. View Article : Google Scholar : PubMed/NCBI
25	Iwakawa R, Kohno T, Kato M, Shiraishi K, Tsuta K, Noguchi M, Ogawa S and Yokota J: MYC amplification as a prognostic marker of early-stage lung adenocarcinoma identified by whole genome copy number analysis. Clin Cancer Res. 17:1481–1489. 2011. View Article : Google Scholar : PubMed/NCBI
26	Ciribilli Y and Borlak J: Oncogenomics of c-Myc transgenic mice reveal novel regulators of extracellular signaling, angiogenesis and invasion with clinical significance for human lung adenocarcinoma. Oncotarget. 8:101808–101831. 2017. View Article : Google Scholar : PubMed/NCBI
27	Wei C and Dong X, Lu H, Tong F, Chen L, Zhang R, Dong J, Hu Y, Wu G and Dong X: LPCAT1 promotes brain metastasis of lung adenocarcinoma by up-regulating PI3K/AKT/MYC pathway. J Exp Clin Cancer Res. 38:952019. View Article : Google Scholar : PubMed/NCBI
28	Fan G, Xu P and Tu P: miR-1827 functions as a tumor suppressor in lung adenocarcinoma by targeting MYC and FAM83F. J Cell Biochem. 121:1675–1689. 2020. View Article : Google Scholar : PubMed/NCBI
29	Cunningham JT, Moreno MV, Lodi A, Ronen SM and Ruggero D: Protein and nucleotide biosynthesis are coupled by a single rate-limiting enzyme, PRPS2, to drive cancer. Cell. 157:1088–1103. 2014. View Article : Google Scholar : PubMed/NCBI
30	Barfeld SJ, Fazli L, Persson M, Marjavaara L, Urbanucci A, Kaukoniemi KM, Rennie PS, Ceder Y, Chabes A, Visakorpi T and Mills IG: Myc-dependent purine biosynthesis affects nucleolar stress and therapy response in prostate cancer. Oncotarget. 6:12587–12602. 2015. View Article : Google Scholar : PubMed/NCBI