Original Article

LncRNA MALAT1 Promote Cell Proliferation and Invasion by sponging miR-125b to Modulate HMGA1 Expression in Laryn-gocarcinoma

Abstract

Background: Laryngocarcinoma is the most frequent head and neck malignant tumor. MALAT1 have a role in promoting cell proliferation and metastasis in several tumors. This research aimed to investigate the great roles of MALAT1in laryngocarcinoma.

Methods: Overall, 54 cases of laryngocarcinoma tissues pathological specimens and paracancerous tissues were collected by surgical resection from the Department of Otolaryngology-Head and Neck Surgery at the Shandong Provincial Hospital affiliated to Shandong University, China from Jan 2012 to Oct 2015. The microRNA and protein levels of genes were evaluated by RT-qPCR and western blot. The proliferative and invasive ability were calculated usingCCK8 and transwell assays. Kaplan-Meier method was used to assess the survival of laryngocarcinoma patients.

Results: In laryngocarcinoma tissues and cells, lncRNA MALAT1 expression was significantly increased compared to normal tissues and cells. LncRNA MALAT1 promotes proliferation and migration of laryngocarcinoma cells. LncRNA MALAT1 upregulates HMGA1 expression by acting as a competitive endogenous RNA (ceRNA) for miR-125b. Rescue experiments showed that microRNA-125b inhibitor reversed the change in cell viability and invasion induced by sh-MALAT1. Down regulation of lncRNA MALAT1 inhibits laryngocarcinoma proliferation and invasion by modulating miR-125b /HMGA1.

Conclusion: LncRNA MALAT1 promotes the development of laryngocarcinoma by regulating the expression level of HMGA1 by acting as a miR-125b ceRNA and may be considered as a new strategy for the development of laryngocarcinoma.

1. Markou K, Christoforidou A, Karasmanis et al (2013). Laryngeal cancer: epidemiologi-cal data from Nuorthern Greece and re-view of the literature. Hippokratia, 17: 313-318.
2. Lampri ES, Chondrogiannis G, Ioachim E et al (2015). Biomarkers of head and neck cancer, tools or a gordian knot? Int J Clin Exp Med, 8: 10340-10357.
3. Iovănescu GH, Poenaru M, Doroş C, et al (2013). Histopathological prognostic and risk factors in patients with laryngeal ne-oplasms. Rom J Morphol Embryol, 54: 1087-1092.
4. Gutschner T, Diederichs S (2012). The hallmarks of cancer: a long non-coding RNA point of view. RNA Biol, 9: 703-719.
5. Kung JT, Colognori D, Lee JT (2013). Long noncoding RNAs: past, present, and fu-ture. Genetics, 193: 651-669.
6. Wapinski O, Chang HY (2011). Long noncoding RNAs and human disease. Trends Cell Biol, 21: 354-361.
7. Cesana M, Cacchiarelli D, Legnini I et al (2011). A long noncoding RNA controls muscle differentiation by functioning as a competing endogenous RNA. Cell, 147: 358-369.
8. Lu J, Getz G, Miska EA et al (2005). Mi-croRNA expression profiles classify hu-man cancers. Nature, 435: 834-838.
9. Gong X, Zhu Y, Chang H, et al (2019). Long noncoding RNA MALAT1 pro-motes cardiomyocyte apoptosis after myocardial infarction via targeting miR-144-3p. Biosci Rep, 39: BSR20191103.
10. Si Y, Yang Z, Ge Q et al (2019). Long non-coding RNA Malat1 activated autophagy, hence promoting cell proliferation and inhibiting apoptosis by sponging miR-101 in colorectal cancer. Cell Mol Biol Lett, 24: 50.
11. Wang XM, Li XM, Song N, et al (2019). Long non-coding RNAs H19, MALAT1 and MIAT as potential novel biomarkers for diagnosis of acute myocardial infarc-tion. Biomed Pharmacother, 118: 109208.
12. Yu X, Li Z (2015). The role of microRNAs expression in laryngeal cancer. Oncotarget, 6: 23297-23305.
13. Li P, Liu H, Wang Z et al (2016). Mi-croRNAs in laryngeal cancer: implications for diagnosis, prognosis and therapy. Am J Transl Res, 8: 1935-1944.
14. Chen YF, Wei YY, Yang CC et al (2019). miR-125b suppresses oral oncogenicity by targeting the anti-oxidative gene PRXL2A. Redox Biol, 22:101140.
15. Xiao T, Zhou Y, Li H et al (2018). MiR-125b suppresses the carcinogenesis of osteosarcoma cells via the MAPK-STAT3 pathway. J Cell Biochem.
16. Li X, Zhang Z, Jiang H et al (2018). Circular RNA circPVT1 Promotes Proliferation and Invasion Through Sponging miR-125b and Activating E2F2 Signaling in Non-Small Cell Lung Cancer. Cell Physiol Biochem, 51: 2324-2340.
17. Fan YX, Bian XH, Qian PD et al (2018). MicroRNA-125b inhibits cell prolifera-tion and induces cell apoptosis in esoph-ageal squamous cell carcinoma by target-ing BMF. Oncol Rep, 40: 61-72.
18. Yuan M, Da Silva ACAL, Arnold A et al (2018). MicroRNA (miR) 125b regulates cell growth and invasion in pediatric low grade glioma. Sci Rep, 8: 12506.
19. Li Y, Wang Y, Fan H, et al (2018). miR-125b-5p inhibits breast cancer cell prolif-eration, migration and invasion by target-ing KIAA1522. Biochem Biophys Res Com-mun, 504: 277-282.
20. Sun B, Zhang Y, Zhou L et al (2019). The proliferation of cervical cancer is promot-ed by miRNA-125b through the regula-tion of the HMGA1. Onco Targets Ther, 12: 2767-2776.
21. Ma W, Cui Y, Liu M, et al (2019). Downreg-ulation of miR-125b promotes resistance of glioma cells to TRAIL through over-expression of Tafazzin which is a mito-chondrial protein. Aging, 11: 2670-2680.
22. Hui L, Zhang J, Guo X (2018). MiR-125b-5p suppressed the glycolysis of laryngeal squamous cell carcinoma by down-regulating hexokinase-2. Biomed Pharma-cother, 103: 1194-1201.
23. Bolha L, Ravnik-Glavac M, Glavac D (2017). Long Noncoding RNAs as Bi-omarkers in Cancer. Dis Markers, 2017: 7243968.
24. Qiu MT, Hu JW, Yin R, et al (2013). Long noncoding RNA: an emerging paradigm of cancer research. Tumour Biol, 34: 613-620.
25. Chen P, Huang Y, Wang Y, et al (2019). MALAT1 overexpression promotes the proliferation of human periodontal liga-ment stem cells by upregulating fibroblast growth factor 2. Exp Ther Med, 18: 1627-1632.
26. Zhu K, Ren Q, Zhao Y (2019). lncRNA MALAT1 overexpression promotes pro-liferation, migration and invasion of gas-tric cancer by activating the PI3K/AKT pathway. Oncol Lett, 17: 5335-5342.
27. Wei S, Wang K, Huang X, et al (2019). LncRNA MALAT1 contributes to non-small cell lung cancer progression via modulating miR-200a-3p/programmed death-ligand 1 axis. Int J Immunopathol Pharmacol, 33: 2058738419859699.
28. Wu XS, Wang F, Li HF et al (2017). LncRNA-PAGBC acts as a microRNA sponge and promotes gallbladder tumor-igenesis. EMBO Rep, 18: 1837-1853.
29. Dai SG, Guo LL, Xia X, et al (2019). Long non-coding RNA WT1-AS inhibits cell aggressiveness via miR-203a-5p/FOXN2 axis and is associated with prognosis in cervical cancer. Eur Rev Med Pharmacol Sci, 23: 486-495.
30. Zhao H, Hu GM, Wang WL, et al (2019). LncRNA TDRG1 functions as an onco-gene in cervical cancer through sponging miR-330-5p to modulate ELK1 expres-sion. Eur Rev Med Pharmacol Sci, 23: 7295-7306.
31. Zhao ZB, Chen F, Bai XF (2019). Long Noncoding RNA MALAT1 Regulates Hepatocellular Carcinoma Growth Under Hypoxia via Sponging MicroRNA-200a. Yonsei Med J, 60: 727-734.
32. Ma P, Li Y, Zhang W et al (2019). Long Non-coding RNA MALAT1 Inhibits Neuron Apoptosis and Neuroinflamma-tion While Stimulates Neurite Outgrowth and Its Correlation With MiR-125b Me-diates PTGS2, CDK5 and FOXQ1 in Alzheimer's Disease. Curr Alzheimer Res, 16: 596-612.
33. El-Khazragy N, Elshimy AA, Hassan SS et al (2018). Dysregulation of miR-125b predicts poor response to therapy in pe-diatric acute lymphoblastic leukemia. J Cell Biochem, doi: 10.1002/jcb.28017. Online ahead of print.
34. Hua S, Quan Y, Zhan M, et al (2019). miR-125b-5p inhibits cell proliferation, migra-tion, and invasion in hepatocellular carci-noma via targeting TXNRD1. Cancer Cell Int, 19: 203.
35. Nie J, Jiang HC, Zhou YC et al (2019). MiR-125b regulates the proliferation and me-tastasis of triple negative breast cancer cells via the Wnt/beta-catenin pathway and EMT. Biosci Biotechnol Biochem, 83: 1062-1071.
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IssueVol 50 No 5 (2021) QRcode
SectionOriginal Article(s)
Published2021-04-30
DOI https://doi.org/10.18502/ijph.v50i5.6113
Keywords
MALAT1 MicroRNA-125b Proliferation Invasion Laryngocarcinoma

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How to Cite
1.
Zong G, Feng X, Sun X, Du J, Wang G, Song T. LncRNA MALAT1 Promote Cell Proliferation and Invasion by sponging miR-125b to Modulate HMGA1 Expression in Laryn-gocarcinoma. Iran J Public Health. 50(5):959-969.