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Zainab Thaer Hameed
Seyyed Meysam Abtahi Froushani


lncRNA MEG-3, Gene expression, oral squamous cell carcinoma, biomarker, Neoplasm


Background: According to previous studies, aberrant expression of various non-coding RNAs, including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), plays undeniable roles in the development and progression of different types of cancer, including OSCC. This study aimed to investigate long non-coding RNA Maternally Expressed 3 (LNC- MEG3) expression patterns as a potential diagnostic biomarker for oral squamous cell carcinoma (OSCC).

Method: In this cross-sectional study, LNC- MEG3 expression patterns were examined using real-time PCR method. Firstly, tumor tissue and margins were separated during surgery in 100 patients. Then total RNA was extracted and transcribed to cDNA from the obtained to measure the transcription level of lnc-MEG3 by qRT-PCR. GraphPad 6 Prism v.8 was used to perform the statistical analyses. Comparisons between groups in internal samples were conducted by paired student's t-test (P < 0.05). 

Results: Our results indicated that the lncRNA MEG3 is downregulated in oral squamous cell carcinoma (OSCC) tumor samples compared to adjacent marginal tissue. These changes were significantly associated with lymph node invasion, tissue differentiation, and metastasis. Also, using receiver operating characteristic curve analysis, the MEG-3 expression pattern was found as a possible diagnostic biomarker for OSCC (The area under the curve was 0.62 and p-value:0.012).

Conclusion: We identified lncRNA MEG-3 downregulation in OSCC tumorigenesis. Our findings suggest lncRNA MEG-3 as a possible biomarker for OSCC.

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1. Pannone G, Santoro A, Papagerakis S, Lo Muzio L, De Rosa G, Bufo P. The role of human papillomavirus in the pathogenesis of head & neck squamous cell carcinoma: an overview. Infect Agent Cancer. 2011;6(1):4.
2. Mehrotra R, Yadav S. Oral squamous cell carcinoma: etiology, pathogenesis and prognostic value of genomic alterations. Indian J Cancer. 2006;43(2):60–6.
3. Patel SC, Carpenter WR, Tyree S, Couch ME, Weissler M, Hackman T, Hayes DN, Shores C, Chera BS. Increasing incidence of oral tongue squamous cell carcinoma in young white women, age 18 to 44 years. J Clin Oncol. 2011;29(11):1488–94.
4. Curry JM, Sprandio J, Cognetti D, Luginbuhl A, Bar-ad V, Pribitkin E, Tuluc M. Tumor microenvironment in head and neck squamous cell carcinoma. Semin Oncol. 2014;41(2):217–34.
5. Gandini S, Botteri E, Iodice S, Boniol M, Lowenfels AB, Maisonneuve P, Boyle P. Tobacco smoking and cancer: a meta-analysis. Int J Cancer. 2008;122(1):155–64.
6. Yamashita T, Kato K, Long NK, Makita H, Yonemoto K, Iida K, Tamaoki N, Hatakeyama D, Shibata T. Effects of smoking and alcohol consumption on 5-fluorouracil-related metabolic enzymes in oral squamous cell carcinoma. Molecular and clinical oncology. 2014;2(3):429–34.
7. Guo LK, Zhang CX, Guo XF. Association of genetic polymorphisms of aldehyde dehydrogenase-2 and cytochrome P450 2E1-RsaI and alcohol consumption with oral squamous cell carcinoma. Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2012;34(4):390–5.
8. Bloebaum M, Poort L, Böckmann R, Kessler P. Survival after curative surgical treatment for primary oral squamous cell carcinoma. J Craniomaxillofac Surg. 2014;42(8):1572–6.
9. Haniye Mohammadrezakhani, Behzad Baradaran,Dariush Shanehbandi Milad Asadi,Shahriar Hashemzadeh, Khalil Hajiasgharzadeh ,Reza Safaralizadeh.Overexpression and Clinicopathological Correlation of Long Noncoding RNA TMPO-AS1 in Colorectal Cancer Patients. J Gastrointest Canc 2020;51, 952–956.
10. Malakoti F, Targhazeh N, Karimzadeh H, Mohammadi E, Asadi M, Asemi Z, et al. Multiple function of lncRNA MALAT1 in cancer occurrence and progression. Chem Biol Drug Des (2021). doi: 10.1111/cbdd.14006.
11. Karimi, D., Pedram, N., Kakaei, F., Asadi, M., Poursaei, E., and Kermani, T. A. (2021). FIS1 Overexpression Is Correlated with Tumor Metastasis in Gastric Adenocarcinoma. J. Gastrointest. Cancer (Online ahead of print). doi:10.1007/ s12029-021-00639-5
12. Behzadi S, Baradaran B, Hosseinpourfeizi MA, Dastmalchi N, Rajabi A, Asadi M, Safaralizadeh R. BC032913 as a novel antisense noncoding RNA is downregulated in gastric cancer. J Gastrointest Cancer. 2021;52(3):928–31.
13. R. Ghodrati, R. Safaralizadeh, N. Dastmalchi, M. Hosseinpourfeizi, M. Asadi, M. Shirmohammadi, B. Baradaran, Overexpression of lncRNA DLEU1 in Gastric Cancer Tissues Compared to Adjacent Non-Tumor Tissues, J Gastrointest Cancer 2022;53:990–994.
14. F.Malakoti, F.Alemi, H.Karimzadeh, Z. Asemi, M.Asadi, H.Ghobadi, J. Soleimanpour, B.Yousefi. Long noncoding RNA-miRNA-mRNA axes multiple roles in osteosarcoma. Gene Reports, 23, 101090.
15. H. Zarredar, M. Asadi, D. Shanehbandi, V. Zafari, S. Bornodeli, Z. Soleimani, et al., Evaluation of the LncRNA TMPO AS-1 expression level in melanoma tissues in comparison to paired normal marginal tissues, Middle East J. Cancer 14 (3) (2023) 399–404.
16. Zhang X, Rice K, Wang Y, Chen W, Zhong Y, Nakayama Y, Zhou Y, Klibanski A. Maternally expressed gene 3 (MEG3) noncoding ribonucleic acid: isoform structure, expression, and functions. Endocrinology. 2010; 151:939–947.
17. Xiu YL, Sun KX, Chen X, Chen S, Zhao Y, Guo QG, Zong ZH. Upregulation of the lncRNA Meg3 induces autophagy to inhibit tumorigenesis and progression of epithelial ovarian carcinoma by regulating activity of ATG3. Oncotarget. 2017; 8:31714–31725.
18. Zhang CY, Yu MS, Li X, Zhang Z, Han CR, Yan B. Overexpression of long non-coding RNA MEG3 suppresses breast cancer cell proliferation, invasion, and angiogenesis through AKT pathway. Tumour Biol. 2017; 39:10104283177013.
19. Zhang J, Lin Z, Gao Y, Yao T. Downregulation of long noncoding RNA MEG3 is associated with poor prognosis and promoter hypermethylation in cervical cancer. J Exp Clin Cancer Res. 2017; 36:5.
20. Zhang J, Yao T, Wang Y, Yu J, Liu Y, Lin Z. Long noncoding RNA MEG3 is downregulated in cervical cancer and affects cell proliferation and apoptosis by regulating miR-21. Cancer Biol Ther. 2016; 17:104–113
21. Zhou X, Ji G, Ke X, Gu H, Jin W, Zhang G. MiR-141 inhibits gastric cancer proliferation by interacting with long noncoding RNA MEG3 and down-regulating E2F3 expression. Dig Dis Sci. 2015; 60:3271–3282.
22. Wu J, Xie H. Expression of long noncoding RNA-HOX transcript antisense intergenic RNA in oral squamous cell carcinoma and effect on cell growth. Tumour Biol. 2015;36(11):8573– 8
23. Tang H, Wu Z, Zhang J, Su B. Salivary lncRNA as a potential marker for oral squamous cell carcinoma diagnosis. Mol Med Rep. 2013;7(3):761 – 6.
24. Li Z, Li C, Liu C, Yu S, Zhang Y. Expression of the long non-coding RNAs MEG3, HOTAIR, and MALAT-1 in non-functioning pituitary adenomas and their relationship to tumor behavior. Pituitary. 2014; 18:42–47.
25. Jia LF, Wei SB, Gan YH, Guo Y, Gong K, Mitchelson K, Cheng J, Yu GY. Expression, regulation and roles of miR- 26a and MEG3 in tongue squamous cell carcinoma. Int J Cancer. 2014; 135:2282–2293.
26. Li J, Zi Y, Wang W, Li Y. LncRNA MEG3 Inhibits Cell Proliferation and Metastasis in Chronic Myeloid Leukemia via Targeting MiR-184. Oncol Res. 2017. http://doi.org/ 10 .3727/096504017X14980882803151.
27. Peng W, Si S, Zhang Q, Li C, Zhao F, Wang F, Yu J, Ma R. Long non-coding RNA MEG3 functions as a competing endogenous RNA to regulate gastric cancer progression. J Exp Clin Cancer Res. 2015; 34:79.
28. Lyu Y, Lou J, Yang Y, Feng J, Hao Y, Huang S, Yin L, Xu J, Huang D, Ma B, Zou D, Wang Y, Zhang Y, et al. Dysfunction of the WT1-MEG3 signaling promotes AML leukemogenesis via p53-dependent and -independent pathways. Leukemia. 2017. http://doi.org/10.1038/ leu.2017.116.
29. Wang, L.; Yu, M.; Zhao, S. lncRNA MEG3 modified epithelial-mesenchymal transition of ovarian cancer cells by sponging miR-219a-5p and regulating EGFR. J. Cell. Biochem. 2019, 120, 17709–17722.
30. Wang, J.; Xu, W.; He, Y.; Xia, Q.; Liu, S. LncRNA MEG3 impacts proliferation, invasion, and migration of ovarian cancer cells through regulating PTEN. Inflamm. Res. 2018, 67, 927–936.
31. Balas, M.; Johnson, A.M. Exploring the mechanisms behind long noncoding RNAs and cancer. Noncoding RNA Res. 2018, 3, 108–117.
32. Zhang, J.; Liu, J.; Xu, X.; Li, L. Curcumin suppresses cisplatin resistance development partly via modulating extracellular vesicle-mediated transfer of MEG3 and miR-214 in ovarian cancer. Cancer Chemother. Pharmacol. 2017, 79, 479–487.