Adipokines Regulate the Expression of Tumor-Relevant MicroRNAs

Overview

Journal Obes Facts

Publisher Karger

Specialty Endocrinology

Date 2019 Apr 19

PMID 30999294

Citations 19

Authors

Simon Jasinski-Bergner

Heike Kielstein

Affiliations

Soon will be listed here.

Abstract

Background: Increasing prevalence of obesity requires the investigation of respective comorbidities, including tumor diseases like colorectal, renal, post-menopausal breast, prostate cancer, and leukemia. To date, molecular mechanisms of the malignant transformation of these peripheral tissues induced by obesity remain unclear. Adipose tissue secretes factors with hormone-like functions, the adipokines, and is therefore categorized as an endocrine organ. Current research demonstrates the ability of adipose tissue to alter DNA methylation and gene expression in peripheral tissues, probably affecting microRNA (miR) expression.

Methods: Literature was analyzed for adipokine-regulated miRs. Many of these adipokine upregulated or downregulated miRs exert either oncogenic or anti-tumoral potential.

Results: The three selected and analyzed adipokines, adiponectin, leptin, and resistin, induce more strongly oncogenic miRs and simultaneously reduce anti-tumoral miRs than vice versa. This effect is not only true for the pure number of regulated miRs, it is also the case by consideration of the abundance of the respective miR expression based on actual data sets derived from next-generation sequencing.

Conclusion: The link of obesity and cancer is analyzed under the aspect of adipokine-regulated miRs. At the same time the impact of miR abundance is considered as a regulatory variable. This context offers new strategies for tumor therapy and diagnostics.

Citing Articles

The adipokines in oral cancer pathogenesis and its potential as a new therapeutic approach.

Wang X, Wang J, Zhao X, Zhang J, Zhang Y Naunyn Schmiedebergs Arch Pharmacol. 2025; .

PMID: 40056203 DOI: 10.1007/s00210-025-03939-w.

The influence of nutritional status, lipid profile, leptin concentration and polymorphism of genes encoding leptin and neuropeptide Y on the effectiveness of immunotherapy in advanced NSCLC patients.

Frak M, Grenda A, Krawczyk P, Kuznar-Kaminska B, Pazdrowski P, Kedra K BMC Cancer. 2024; 24(1):937.

PMID: 39090596 PMC: 11295594. DOI: 10.1186/s12885-024-12716-6.

Epigenetic modifications in obesity-associated diseases.

Long Y, Mao C, Liu S, Tao Y, Xiao D MedComm (2020). 2024; 5(2):e496.

PMID: 38405061 PMC: 10893559. DOI: 10.1002/mco2.496.

The Role of Adipokines in Tumor Progression and Its Association with Obesity.

Kim J, Kim J, Lee Y Biomedicines. 2024; 12(1).

PMID: 38255203 PMC: 10813163. DOI: 10.3390/biomedicines12010097.

Exploring the role of the inflammasomes on prostate cancer: Interplay with obesity.

Perez-Gomez J, Montero-Hidalgo A, Fuentes-Fayos A, Sarmento-Cabral A, Guzman-Ruiz R, Malagon M Rev Endocr Metab Disord. 2023; 24(6):1165-1187.

PMID: 37819510 PMC: 10697898. DOI: 10.1007/s11154-023-09838-w.

References

Zhu L, Shi C, Ji C, Xu G, Chen L, Yang L . FFAs and adipokine-mediated regulation of hsa-miR-143 expression in human adipocytes. Mol Biol Rep. 2013; 40(10):5669-75. DOI: 10.1007/s11033-013-2668-2. View

Sadashiv , Tiwari S, Paul B, Kumar S, Chandra A, Dhananjai S . Over expression of resistin in adipose tissue of the obese induces insulin resistance. World J Diabetes. 2012; 3(7):135-41. PMC: 3399912. DOI: 10.4239/wjd.v3.i7.135. View

Schraw T, Wang Z, Halberg N, Hawkins M, Scherer P . Plasma adiponectin complexes have distinct biochemical characteristics. Endocrinology. 2008; 149(5):2270-82. PMC: 2329278. DOI: 10.1210/en.2007-1561. View

Hamrick M, Herberg S, Arounleut P, He H, Shiver A, Qi R . The adipokine leptin increases skeletal muscle mass and significantly alters skeletal muscle miRNA expression profile in aged mice. Biochem Biophys Res Commun. 2010; 400(3):379-83. PMC: 3740337. DOI: 10.1016/j.bbrc.2010.08.079. View

Larsson S, Wolk A . Overweight and obesity and incidence of leukemia: a meta-analysis of cohort studies. Int J Cancer. 2007; 122(6):1418-21. DOI: 10.1002/ijc.23176. View

Mu W, Hu C, Zhang H, Qu Z, Cen J, Qiu Z . miR-27b synergizes with anticancer drugs via p53 activation and CYP1B1 suppression. Cell Res. 2015; 25(4):477-95. PMC: 4387554. DOI: 10.1038/cr.2015.23. View

Wen F, Li B, Huang C, Wei Z, Zhou Y, Liu J . MiR-34a is Involved in the Decrease of ATP Contents Induced by Resistin Through Target on ATP5S in HepG2 Cells. Biochem Genet. 2015; 53(11-12):301-9. DOI: 10.1007/s10528-015-9693-x. View

Okamoto Y, Folco E, Minami M, Wara A, Feinberg M, Sukhova G . Adiponectin inhibits the production of CXC receptor 3 chemokine ligands in macrophages and reduces T-lymphocyte recruitment in atherogenesis. Circ Res. 2007; 102(2):218-25. DOI: 10.1161/CIRCRESAHA.107.164988. View

Cohen S, Gammon M, Signorello L, North K, Lange E, Fowke J . Serum adiponectin in relation to body mass index and other correlates in black and white women. Ann Epidemiol. 2010; 21(2):86-94. PMC: 3018848. DOI: 10.1016/j.annepidem.2010.10.011. View

10.

Jasinski-Bergner S, Mandelboim O, Seliger B . The role of microRNAs in the control of innate immune response in cancer. J Natl Cancer Inst. 2014; 106(10). DOI: 10.1093/jnci/dju257. View

11.

Yang W, Chang A, Wang S, Wang S, Chang Y, Chang T . Leptin promotes VEGF-C production and induces lymphangiogenesis by suppressing miR-27b in human chondrosarcoma cells. Sci Rep. 2016; 6:28647. PMC: 4921910. DOI: 10.1038/srep28647. View

12.

Tartaglia L, Dembski M, Weng X, Deng N, Culpepper J, Devos R . Identification and expression cloning of a leptin receptor, OB-R. Cell. 1995; 83(7):1263-71. DOI: 10.1016/0092-8674(95)90151-5. View

13.

Roberts D, Dive C, Renehan A . Biological mechanisms linking obesity and cancer risk: new perspectives. Annu Rev Med. 2009; 61:301-16. DOI: 10.1146/annurev.med.080708.082713. View

14.

Tsai C, Tsai H, Huang H, Hung C, Hsu C, Fong Y . Resistin promotes tumor metastasis by down-regulation of miR-519d through the AMPK/p38 signaling pathway in human chondrosarcoma cells. Oncotarget. 2014; 6(1):258-70. PMC: 4381593. DOI: 10.18632/oncotarget.2724. View

15.

Wrann C, Laue T, Hubner L, Kuhlmann S, Jacobs R, Goudeva L . Short-term and long-term leptin exposure differentially affect human natural killer cell immune functions. Am J Physiol Endocrinol Metab. 2011; 302(1):E108-16. DOI: 10.1152/ajpendo.00057.2011. View

16.

Fasshauer M, Bluher M . Adipokines in health and disease. Trends Pharmacol Sci. 2015; 36(7):461-70. DOI: 10.1016/j.tips.2015.04.014. View

17.

Kern P, Di Gregorio G, Lu T, Rassouli N, Ranganathan G . Adiponectin expression from human adipose tissue: relation to obesity, insulin resistance, and tumor necrosis factor-alpha expression. Diabetes. 2003; 52(7):1779-85. DOI: 10.2337/diabetes.52.7.1779. View

18.

Kozomara A, Griffiths-Jones S . miRBase: annotating high confidence microRNAs using deep sequencing data. Nucleic Acids Res. 2013; 42(Database issue):D68-73. PMC: 3965103. DOI: 10.1093/nar/gkt1181. View

19.

Teixeira L, Leonel A, Aguilar E, Batista N, Alves A, Coimbra C . The combination of high-fat diet-induced obesity and chronic ulcerative colitis reciprocally exacerbates adipose tissue and colon inflammation. Lipids Health Dis. 2011; 10:204. PMC: 3254137. DOI: 10.1186/1476-511X-10-204. View

20.

Faggioni R, Jones-Carson J, Reed D, Dinarello C, Feingold K, Grunfeld C . Leptin-deficient (ob/ob) mice are protected from T cell-mediated hepatotoxicity: role of tumor necrosis factor alpha and IL-18. Proc Natl Acad Sci U S A. 2000; 97(5):2367-72. PMC: 15807. DOI: 10.1073/pnas.040561297. View