The miR-383-LDHA axis regulates cell proliferation, invasion and glycolysis in hepatocellular cancer

Document Type : Original Article

Authors

1 Department of Infectious Disease, XiangTan City Central Hospital, XiangTan, People's Republic of China

2 Edong Healthcare City Hospital of Traditional Chinese Medicine, Inefections Disease Hospital, Huangshi, People's Republic of China

3 Cancer Research Institute, University of South China, Key Laboratory of Cancer Cellular and Molecular Pathology of Hunan Provincial University, Hengyang, People's Republic of China

Abstract

Objective(s): To explore the correlation between expression patterns and functions of miR-383 and LDHA in hepatocellular cancer (HCC).
Materials and Methods: We detected the expression of miR-383 and LDHA in 30 HCC tissues and their matched adjacent normal tissues using qRT-PCR. Then we performed MTT assay, foci formation assay, transwell migration assay, glucose uptake assay and lactate production assay to explore the function of miR-383 in cell proliferation, invasion and glycolysis in HCC cell lines. Luciferase reporter assay was used to explore whether LDHA was a target gene of miR-383. Western blot and qRT-PCR were used to further confirm LDHA was targeted by miR-383. Then the above functional experiments were repeated to see whether the function of LDHA could be inhibited by miR-383.
Results: The results of qRT-PCR showed that miR-383 was down-regulated in HCC tissues compared with their matched adjacent normal tissues. Functional experiments showed that overexpression of miR-383 significantly suppressed cell proliferation, invasion and glycolysis. Luciferase reporter assay showed LDHA was a target gene of miR-383 and expression of LDHA was inversely correlated with that of miR-383 in HCC. Besides, increased cell proliferation, invasion and glycolysis triggered by LDHA could be inhibited by overexpression of miR-383 in HCC cell lines.
Conclusion: Our study proved that miR-383 is down-regulated in HCC and acts as a tumor suppressor through targeting LDHA. Targeting the miR-383-LDHA axis might be a promising strategy in HCC treatment.

Keywords

References

1. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin 2015; 65:87-108.
2. Tabrizian P, Roayaie S, Schwartz ME. Current management of hepatocellular carcinoma. World J Gastroenterol 2014; 20:10223-1237.
3.   Mikhail S, Cosgrove D, Zeidan A. Hepatocellular carcinoma: systemic therapies and future perspectives. Expert Rev Anticancer Ther. 2014; 14:1205-1218.
4. Raza A, Sood GK. Hepatocellular carcinoma review: current treatment, and evidence-based medicine. World J Gastroenterol 2014; 20:4115-4127.
5. Bruix J, Gores GJ, Mazzaferro V. Hepatocellular carcinoma: clinical frontiers and perspectives. Gut 2014; 63:844-855.
6. Bartel DP. MicroRNAs: target recognition and regulatory functions. Cell 2009; 136:215-233.
7. Farazi TA, Hoell JI, Morozov P, Tuschl T. MicroRNAs in human cancer. Adv Exp Med Biol 2013; 774:1-20.
8. Blandino G, Fazi F, Donzelli S, Kedmi M, Sas-Chen A, Muti P, et al. Tumor suppressor microRNAs: A novel non-coding alliance against cancer. FEBS Lett 2014; 588:2639-2652.
9. Wang X, Ren Y, Wang Z, Xiong X, Han S, Pan W, et al. Down-regulation of 5S rRNA by miR-150 and miR-383 enhances c-Myc-rpL11 interaction and inhibits proliferation of esophageal squamous carcinoma cells. FEBS Lett 2015; 589:3989-3997.
10. He ZW, Cen DY, Luo XY, Li DF, Li PG, Liang LY, et al. Downregulation of miR-383 promotes glioma cell invasion by targeting insulin-like growth factor 1 receptor. Med Oncol 2013; 30:557.
11. Xu Z, Zeng X, Tian D, Xu H, Cai Q, Wang J, et al. MicroRNA-383 inhibits anchorage-independent growth and induces cell cycle arrest of glioma cells by targeting CCND1. Biochem Biophys Res Commun 2014; 453:833-838.
12. Xu D, Ma P, Gao G, Gui Y, Niu X, Jin B. MicroRNA-383 expression regulates proliferation, migration, invasion, and apoptosis in human glioma cells. Tumour Biol 2015; 36:7743-7753.
13. Lian J, Tian H, Liu L, Zhang XS, Li WQ, Deng YM, et al. Downregulation of microRNA-383 is associated with male infertility and promotes testicular embryonal carcinoma cell proliferation by targeting IRF1. Cell Death Dis 2010; 1:e94.
14. Huang HL, Tian H, Duan ZZ, Cao YX, Zhang XS, Sun F. microRNA-383 impairs phosphorylation of H2AX by targeting PNUTS and inducing cell cycle arrest in testicular embryonal carcinoma cells. Cell Signalling 2014; 26:903-911.
15. Li KK, Pang JC, Lau KM, Zhou L, Mao Y, Wang Y, et al. MiR-383 is Downregulated in Medulloblastoma and Targets Peroxiredoxin 3 (PRDX3). Brain Pathol 2013; 23:413-425.
16. Chen L, Guan H, Gu C, Cao Y, Shao J, Wang F. MiR-383 inhibits hepatocellular carcinoma cell proliferation via targeting APRIL. Tumour Biol 2016;37:2497-507.
17. Cai Z, Zhao JS, Li JJ, Peng DN, Wang XY, Chen TL, et al. A combined proteomics and metabolomics profiling of gastric cardia cancer reveals characteristic dysregulations in glucose metabolism. Mol Cell Proteomics 2010; 9:2617-2628.
18. Girgis H, Masui O, White NMA, Scorilas A, Rotondo F, Seivwright A, et al. Lactate Dehydrogenase A is a potential prognostic marker in clear cell renal cell carcinoma. Mol Cancer 2014; 13:101.
19. Girgis H, Masui O, White NM, Scorilas A, Rotondo F, Seivwright A, et al. Lactate dehydrogenase A is a potential prognostic marker in clear cell renal cell carcinoma. Mol Cancer 2014; 13:101.
20. Cui J, Shi M, Xie D, Wei D, Jia Z, Zheng S, et al. FOXM1 promotes the warburg effect and pancreatic cancer progression via transactivation of LDHA expression. Clin Cancer Res 2014; 20:2595-2606.
21. Rong YF, Wu WC, Ni XL, Kuang TT, Jin DY, Wang DS, et al. Lactate dehydrogenase A is overexpressed in pancreatic cancer and promotes the growth of pancreatic cancer cells. Tumor Biol 2013; 34:1523-1530.
22. Yao F, Zhao TJ, Zhong CX, Zhu J, Zhao H. LDHA is necessary for the tumorigenicity of esophageal squamous cell carcinoma. Tumor Biol 2013; 34:25-31.
23. Wang J, Wang H, Liu AF, Fang CG, Hao JG, Wang ZH. Lactate dehydrogenase A negatively regulated by miRNAs promotes aerobic glycolysis and is increased in colorectal cancer. Oncotarget 2015; 6:19456-19468.
24. Rasool M, Rashid S, Arooj M, Ansari SA, Khan KM, Malik A, et al. New possibilities in hepatocellular carcinoma treatment. Anticancer Res 2014; 34:1563-1571.
25. D'Anzeo M, Faloppi L, Scartozzi M, Giampieri R, Bianconi M, Del Prete M, et al. The role of micro-RNAs in hepatocellular carcinoma: from molecular biology to treatment. Molecules 2014; 19:6393-6406.
26. Hung CH, Chiu YC, Chen CH, Hu TH. MicroRNAs in hepatocellular carcinoma: carcinogenesis, progression, and therapeutic target. Biomed Res Int 2014; 2014:486407.
Iranian Journal of Basic Medical Sciences
Volume 20, Issue 2
February 2017
Pages 187-192

Files

Share

How to cite

Statistics