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Cancer Cell International
Published in: Cancer Cell International 1/2019

Open Access 01-12-2019 | NSCLC | Primary research

miR-21 promotes non-small cell lung cancer cells growth by regulating fatty acid metabolism

Authors: Kewei Ni, Dimin Wang, Heyun Xu, Fuyang Mei, Changhao Wu, Zhifang Liu, Bing Zhou

Published in: Cancer Cell International | Issue 1/2019

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Abstract

Background

Lung cancer is one of the most common malignant tumors worldwide. CD36 is a receptor for fatty acids and plays an important role in regulating fatty acid metabolism, which is closely related to tumorigenesis and development. The regulation of miR-21 and its role in tumorigenesis have been extensively studied in recent years. However, the relationship between miR-21 and CD36 regulated fatty acid metabolism in human non-small cell lung cancer remains unknown.

Methods

In this study, lentivirus transfection, qRT-PCR, cell migration, immunofluorescence, and western blot were used to examine the relationship between miR-21 and CD36 regulated fatty acid metabolism and the regulation role of miR-21 in human non-small cell lung cancer.

Results

This study demonstrated that up-regulation of miR-21 promoted cell migration and cell growth in human non-small cell lung cancer cells. Moreover, the intracellular contents of lipids including cellular content of phospholipids, neutral lipids content, cellular content of triglycerides were significantly increased following miR-21 mimic treatment compared with control, and the levels of key lipid metabolic enzymes FASN, ACC1 and FABP5 were obviously enhanced in human non-small cell lung cancer cells. Furthermore, down-regulation of CD36 suppressed miR-21 regulated cell growth, migration and intracellular contents of lipids in human non-small cell lung cancer cells, which suggested that miR-21 promoted cell growth and migration of human non-small cell lung cancer cells through CD36 mediated fatty acid metabolism. Inhibition of miR-21 was revealed to inhibit cell growth, migration, intracellular contents of lipids, and CD36 protein expression level in human non-small cell lung cancer cells. In addition, PPARGC1B was a direct target of miR-21, and down-regulation of PPARGC1B reversed the inhibition of CD36 expression induced by miR-21 inhibitor.

Conclusions

These results explored the mechanism of miR-21 promoted non-small cell lung cancer and might provide a novel therapeutic method in treating non-small cell lung cancer in clinic.
Literature
1.
Remon J, Ahn MJ, Girard N, Johnson M, Kim DW, Lopes G, Pillai RN, Solomon B, Villacampa G, Zhou Q. Advanced stage non-small cell lung cancer: advances in thoracic oncology 2018. Journal Thorac Oncol. 2019;14(7):1134–55.CrossRef
2.
Blandin Knight S, Crosbie PA, Balata H, Chudziak J, Hussell T, Dive C. Progress and prospects of early detection in lung cancer. Open Biol. 2017;7(9):170070.PubMedPubMedCentralCrossRef
3.
Jakobsen E, Rasmussen TR, Green A. Mortality and survival of lung cancer in Denmark: results from the Danish Lung Cancer Group 2000–2012. Acta Oncol. 2016;55(Suppl 2):2–9.PubMedCrossRef
4.
Janssen-Heijnen ML, van Erning FN, De Ruysscher DK, Coebergh JW, Groen HJ. Variation in causes of death in patients with non-small cell lung cancer according to stage and time since diagnosis. Ann Oncol. 2015;26(5):902–7.PubMedCrossRef
5.
6.
Tian K, Shi R, Gu A, Pennella M, Gu LQ. Polycationic probe-guided nanopore single-molecule counter for selective miRNA detection. Methods Mol Biol. 2017;1632:255–68.PubMedPubMedCentralCrossRef
7.
Sandiford OA, Moore CA, Du J, Boulad M, Gergues M, Eltouky H, Rameshwar P. Human aging and cancer: role of miRNA in tumor microenvironment. Adv Exp Med Biol. 2018;1056:137–52.PubMedCrossRef
8.
Qin X, Xu H, Gong W, Deng W. The tumor cytosol miRNAs, fluid miRNAs, and exosome miRNAs in lung cancer. Front Oncol. 2014;4:357.PubMed
9.
Hermansen SK, Nielsen BS, Aaberg-Jessen C, Kristensen BW. miR-21 is linked to glioma angiogenesis: a co-localization study. J Histochem Cytochem. 2016;64(2):138–48.PubMedCrossRef
10.
Xu Z, Liu X, Wang H, Li J, Dai L, Li J, Dong C. Lung adenocarcinoma cell-derived exosomal miR-21 facilitates osteoclastogenesis. Gene. 2018;666:116–22.PubMedCrossRef
11.
Wang W, Songlin P, Sun Y, Zhang B, Jinhui W. miR-21 inhibitor sensitizes human OSCC cells to cisplatin. Mol Biol Rep. 2012;39(5):5481–5.PubMedCrossRef
12.
Frankel LB, Christoffersen NR, Jacobsen A, Lindow M, Krogh A, Lund AH. Programmed cell death 4 (PDCD4) is an important functional target of the microRNA miR-21 in breast cancer cells. J Biol Chem. 2008;283(2):1026–33.PubMedCrossRef
13.
Liu L, Chen Q, Lai R, Wu X, Wu X, Liu F, Xu G, Ji Y. Elevated expression of mature miR-21 and miR-155 in cancerous gastric tissues from Chinese patients with gastric cancer. J Biomed Res. 2010;24(3):187–97.PubMedPubMedCentralCrossRef
14.
Huang CS, Yu W, Cui H, Wang YJ, Zhang L, Han F, Huang T. Increased expression of miR-21 predicts poor prognosis in patients with hepatocellular carcinoma. Int J Clin Exp Pathol. 2015;8(6):7234–8.PubMedPubMedCentral
15.
Su C, Cheng X, Li Y, Han Y, Song X, Yu D, Cao X, Liu Z. MiR-21 improves invasion and migration of drug-resistant lung adenocarcinoma cancer cell and transformation of EMT through targeting HBP1. Cancer Med. 2018;7(6):2485–503.PubMedPubMedCentralCrossRef
16.
Bermudez-Cardona J, Velasquez-Rodriguez C. Profile of free fatty acids and fractions of phospholipids, cholesterol esters and triglycerides in serum of obese youth with and without metabolic syndrome. Nutrients. 2016;8(2):54.PubMedPubMedCentralCrossRef
17.
Kuang YL, Paulson KE, Lichtenstein AH, Lamon-Fava S. Regulation of the expression of key genes involved in HDL metabolism by unsaturated fatty acids. Br J Nutr. 2012;108(8):1351–9.PubMedCrossRef
18.
Huang T, Hu X, Khan N, Yang J, Li D. Effect of polyunsaturated fatty acids on homocysteine metabolism through regulating the gene expressions involved in methionine metabolism. Scientific World J. 2013;2013:931626.
19.
Matthews GM, Howarth GS, Butler RN. Short-chain fatty acids induce apoptosis in colon cancer cells associated with changes to intracellular redox state and glucose metabolism. Chemotherapy. 2012;58(2):102–9.PubMedCrossRef
20.
Balaban S, Lee LS, Varney B, Aishah A, Gao Q, Shearer RF, Saunders DN, Grewal T, Hoy AJ. Heterogeneity of fatty acid metabolism in breast cancer cells underlies differential sensitivity to palmitate-induced apoptosis. Mol Oncol. 2018;12(9):1623–38.PubMedPubMedCentralCrossRef
21.
22.
Shang C, Wang W, Liao Y, Chen Y, Liu T, Du Q, Huang J, Liang Y, Liu J, Zhao Y, et al. LNMICC promotes nodal metastasis of cervical cancer by reprogramming fatty acid metabolism. Can Res. 2018;78(4):877–90.CrossRef
23.
Chen YP, Kuo WW, Baskaran R, Day CH, Chen RJ, Wen SY, Ho TJ, Padma VV, Kuo CH, Huang CY. Acute hypoxic preconditioning prevents palmitic acid-induced cardiomyocyte apoptosis via switching metabolic GLUT4-glucose pathway back to CD36-fatty acid dependent. J Cell Biochem. 2018;119(4):3363–72.PubMedCrossRef
24.
Zhao L, Varghese Z, Moorhead JF, Chen Y, Ruan XZ. CD36 and lipid metabolism in the evolution of atherosclerosis. Br Med Bull. 2018;126(1):101–12.PubMedCrossRef
25.
Pennathur S, Pasichnyk K, Bahrami NM, Zeng L, Febbraio M, Yamaguchi I, Okamura DM. The macrophage phagocytic receptor CD36 promotes fibrogenic pathways on removal of apoptotic cells during chronic kidney injury. Am J Pathol. 2015;185(8):2232–45.PubMedPubMedCentralCrossRef
26.
Sp N, Kang DY, Kim DH, Park JH, Lee HG, Kim HJ, Darvin P, Park YM, Yang YM. Nobiletin inhibits CD36-dependent tumor angiogenesis, migration, invasion, and sphere formation through the Cd36/Stat3/Nf-Kappab signaling axis. Nutrients. 2018;10(6):772.PubMedCentralCrossRef
27.
Nath A, Chan C. Genetic alterations in fatty acid transport and metabolism genes are associated with metastatic progression and poor prognosis of human cancers. Scientific Rep. 2016;6:18669.CrossRef
28.
Pascual G, Avgustinova A, Mejetta S, Martin M, Castellanos A, Attolini CS, Berenguer A, Prats N, Toll A, Hueto JA, et al. Targeting metastasis-initiating cells through the fatty acid receptor CD36. Nature. 2017;541(7635):41–5.PubMedCrossRef
29.
Khaidakov M, Mehta JL. Oxidized LDL triggers pro-oncogenic signaling in human breast mammary epithelial cells partly via stimulation of MiR-21. PLoS ONE. 2012;7(10):e46973.PubMedPubMedCentralCrossRef
30.
Zhao J, Zhi Z, Wang C, Xing H, Song G, Yu X, Zhu Y, Wang X, Zhang X, Di Y. Exogenous lipids promote the growth of breast cancer cells via CD36. Oncol Rep. 2017;38(4):2105–15.PubMedPubMedCentralCrossRef
31.
Calo N, Ramadori P, Sobolewski C, Romero Y, Maeder C, Fournier M, Rantakari P, Zhang FP, Poutanen M, Dufour JF, et al. Stress-activated miR-21/miR-21* in hepatocytes promotes lipid and glucose metabolic disorders associated with high-fat diet consumption. Gut. 2016;65(11):1871–81.PubMedCrossRef
32.
Landberg N, von Palffy S, Askmyr M, Lilljebjorn H, Sanden C, Rissler M, Mustjoki S, Hjorth-Hansen H, Richter J, Agerstam H, et al. CD36 defines primitive chronic myeloid leukemia cells less responsive to imatinib but vulnerable to antibody-based therapeutic targeting. Haematologica. 2018;103(3):447–55.PubMedPubMedCentralCrossRef
33.
Pepino MY, Kuda O, Samovski D, Abumrad NA. Structure-function of CD36 and importance of fatty acid signal transduction in fat metabolism. Annu Rev Nutr. 2014;34:281–303.PubMedPubMedCentralCrossRef
34.
Chevrot M, Martin C, Passilly-Degrace P, Besnard P. Role of CD36 in oral and postoral sensing of lipids. Handb Exp Pharmacol. 2012;209:295–307.CrossRef
35.
Lian J, Guo J, Huang X, Yang XI, Huang G, Mao H, Sun HH, Ba Y, Zhou J. miRNAs regulate hERG. J Cardiovasc Electrophysiol. 2016;27(12):1472–82.PubMedCrossRef
36.
Baldan A, Fernandez-Hernando C. Truths and controversies concerning the role of miRNAs in atherosclerosis and lipid metabolism. Curr Opin Lipidol. 2016;27(6):623–9.PubMedPubMedCentralCrossRef
37.
Zhang HF, Wang YC, Han YD. MicroRNA34a inhibits liver cancer cell growth by reprogramming glucose metabolism. Mol Med Rep. 2018;17(3):4483–9.PubMedPubMedCentral
38.
Cruz-Gil S, Sanchez-Martinez R, Gomez de Cedron M, Martin-Hernandez R, Vargas T, Molina S, Herranz J, Davalos A, Reglero G, Ramirez de Molina A. Targeting the lipid metabolic axis ACSL/SCD in colorectal cancer progression by therapeutic miRNAs: miR-19b-1 role. J Lipid Res. 2018;59(1):14–24.PubMedCrossRef
39.
Cheng L, Zhu Y, Han H, Zhang Q, Cui K, Shen H, Zhang J, Yan J, Prochownik E, Li Y. MicroRNA-148a deficiency promotes hepatic lipid metabolism and hepatocarcinogenesis in mice. Cell Death Dis. 2017;8(7):e2916.PubMedPubMedCentralCrossRef
40.
Metadata
Title
miR-21 promotes non-small cell lung cancer cells growth by regulating fatty acid metabolism
Authors
Kewei Ni
Dimin Wang
Heyun Xu
Fuyang Mei
Changhao Wu
Zhifang Liu
Bing Zhou
Publication date
01-12-2019
Publisher
BioMed Central
Keywords
NSCLC
NSCLC
Published in
Cancer Cell International / Issue 1/2019
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-019-0941-8

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