Deregulation of microRNAs in Head and Neck Cancer Patients
Objectives: Head and neck cancer is amongst the most prevalent malignancies in the world. The condition is also alarming in Pakistan. The main aim of the current research was to examine the expression profiling of microRNAs which are miR-105-5p, miR-10a-5p, miR-3658, miR-3160-3p, miR-4795-5p and miR-431-5p in HNC patients. Furthermore, the expression was also correlated with the clinical parameters, and prognostic significance was evaluated.
Methods: 300 HNC patients tumor samples and an equal number of healthy control samples were collected from differ- ent hospitals in Pakistan. The expression analysis of the selected microRNAs was carried out using real-time PCR (qPCR).
Results: The results showed that the microRNAs were significantly deregulated in HNC patients compared to the con- trols. miR-105-5p (p<0.0004), miR-10a-5p (p<0.0001), miR-3658(p<0.003), miR-3160-3p (p<0.0001) were found signifi- cantly downregulated, while miR-4795-5p (p<0.0001) and miR-431-5p (p<0.0001) were found upregulated in HNC pa- tients as compared to controls. The Kaplan-Meier analysis showed that the deregulation of these microRNAs was found associated with decreased survival in HNC patients.
Conclusion: Our results suggested that the selected microRNAs were found deregulated in HNC patients and this deregulation was also found associated with significantly increased risk of HNC not only that it was also linked to de- creased survival of HNC patients.
1. Cho JK, Hyun SH, Choi N, Kim MJ, PaderaTP, Choi JY, et al. Sig- nificance of lymph node metastasis in cancer dissemination of head and neck cancer. Trans Oncol 2015;8(2):119 –25.
2. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Es- timates of worldwide burden of cancer in 2008: GLOBOCAN
2008. International journal of cancer. 2010;127(12):2893–917.
3. Mohsin Z, Faiq A, NaqviT, Rehman S, Ahmed SI, Farrukh K, et al. Evaluation of head and neck cancer knowledge among the at-risk population of Karachi, Pakistan: A cross-sectional sur- vey. J Health Res 2021;36(4):725–37.
4. Nagadia R, Pandit P, Coman WB, Cooper-White J, Punyadeera
C. miRNAs in head and neck cancer revisited. Cell Oncol 2013;36(1):1–7.
5. Cieślik M, Chinnaiyan AM. Cancer transcriptome profiling at the juncture of clinical translation. NatrRev Gen 2018;19(2):93– 109.
6. Tran N,O'Brien CJ, Clark J, Rose B. Potential role of micro‐RNAs in head and neck tumorigenesis. Head Neck 2010;32(8):1099– 111.
7. Hayes J, Peruzzi PP, Lawler S. MicroRNAs in cancer: Biomarkers, functions and therapy. Trend Mol Med 2014;20(8):460–9.
8. Friedman RC, Farh KKH, Burge CB, Bartel DP. Most mamma- lian mRNAs are conserved targets of microRNAs. Gen Res 2009;19(1):92–105.
9. ChildsG, FazzariM, Kung G, Kawachi N, Brandwein-GenslerM, McLemore M, et al. Low-level expression of microRNAs let-7d and miR-205 are prognostic markers of head and neck squa- mous cell carcinoma. Am J Pathol 2009;174(3):736–45.
10. Hui AB, Lenarduzzi M, Krushel T, Waldron L, Pintilie M, Shi W, et al. Comprehensive MicroRNA profiling for head and neck squamous cell carcinomas. Clin Cancer Res 2010;16(4):1129– 39.
11. Janssen HL, Reesink HW, Lawitz EJ, Zeuzem S, Rodriguez-Tor- res M, Patel K, et al. Treatment of HCV infection by targeting microRNA. New England J Med 2013;368(18):1685–94.
12. Masood N, Malik FA, Kayani MA. Expression of xenobiotic me- tabolizing genes in head and neck cancer tissues. Asian Pac J Cancer Prev 2011;12(2):377–82.
13. Chen Z,Jin Y, Yu D, Wang A, Mahjabeen I, Wang C, et al. Down- regulation of the microRNA-99 family members in head and necksquamous cell carcinoma. Oral Oncol 2012;48(8):686–91.
14. Suh Y, Amelio I, Urbano TG, Tavassoli M. Clinical update on cancer: Molecular oncology of head and neck cancer. Cell Death Dis 2014;5(1):e1018.
15. Masood N, Kayani MA. Mutational analysis of xenobiotic me- tabolizing genes (CYP1A1 and GSTP1) in sporadic head and neck cancer patients. Gen Mol Biol 2011;34:533–8.
16. Pervez S, Jabbar AA, Haider G, Ashraf S, Qureshi MA, Lateef F, et al. Karachi Cancer Registry (KCR): Age-standardized inci- dence rate by age-group and gender in a Mega city of Paki- stan. Asian Pac J Cancer Prev 2020;21(11):3251.
17. Akram S, Mirza T, Mirza MA, Qureshi M. Emerging patterns in clinico-pathological spectrum of oral cancers. Pakistan J Med Sci 2013;29(3):783.
18. Chaudhry S, Khan AA, Mirza KM, Iqbal HA, Masood Y, Khan NR, et al. Estimating the burden of head and neck cancers in the public health sector of Pakistan. Asian Pac J Cancer Prev 2008;9(3):529–32.
19. Zeng Y, Cullen BR. The biogenesis and function of MicroRNAs. Gene Expression and Regulation. Springer, 2006, p. 481–92.
20. Svoronos AA, Engelman DM, Slack FJ. OncomiR or tumor sup- pressor? The duplicity of microRNAs in cancer. Cancer Res 2016;76(13):3666–70.
21. Michael MZ, O'Connor SM, van Holst Pellekaan NG, Young GP, James RJ. Reduced accumulation of specific microRNAs in colorectal neoplasia. Mol Cancer Res 2003;1(12):882–91.
22. Filipowicz W, Bhattacharyya SN, Sonenberg N. Mechanisms of post-transcriptional regulation by microRNAs: Are the an- swers insight? Nat Rev Gen 2008;9(2):102–14.
23. Mahn R, Heukamp LC, Rogenhofer S, von Ruecker A, Müller SC, Ellinger J. Circulating microRNAs (miRNA) in serum of pa- tients with prostate cancer. Urology 2011;77(5):1265. e9–16.
24. Dong X, Chang M, Song X, Ding S, Xie L, Song X. Plasma miR‐ 1247‐5p, miR‐301b‐3pand miR‐105‐5p as potential biomark- ers for early diagnosis of non‐small cell lung cancer. Thorac Cancer 2021;12(4):539–48.
25. Shen Z, Zhou R, Liu C, Wang Y, Zhan W, Shao Z, et al. MicroR- NA-105 is involved in TNF-α-related tumor microenvironment enhanced colorectal cancer progression. Cell Death Disease 2017;8(12):1–13.
26. AraiT, Okato A, Kojima S, IdichiT, Koshizuka K, KurozumiA, et al. Regulation of spindle and kinetochore‐associated protein 1 by antitumor miR‐10a‐5pin renal cell carcinoma. Cancer Sci 2017;108(10):2088–101.
27. Liu LJ, Sun XY, Yang CX, Zou XY. MiR‐10a‐5p restrains the ag- gressive phenotypes of ovarian cancer cells by inhibiting HOXA1. Kaohsiung J Med Sci 2021;37(4):276–85.
28. Bao M, Pan S, Yang W, Chen S, ShanY, Shi H. Serum miR-10a-5p and miR-196a-5p as non-invasive biomarkers in non-small cell lung cancer. IntJ Clin Exp Pathol 2018;11(2):773.
29. Gao L, Yang X, Zhang H,Yu M, Long J, Yang T. Inhibition of miR- 10a-5p suppresses cholangiocarcinoma cell growth through downregulation of Akt pathway. OncoTargets Therapy 2018;11:6981.
30. Hosseini F, Soltani BM, Baharvand H, Hosseinkhani S. Hsa- miR-3658 down-regulates OCT4 gene expression followed by suppressing SW480 cell proliferation and migration. Biochem J 2020;477(12):2281–93.
31. LuanT, Zou R, Huang L, Li N, Fu S, Huang Y, et al. Hsa-miR-3658 promotes cell proliferation, migration and invasion by effect- ing LASS2 in bladder cancer. Clin Lab 2018;64(4):515–25.
32. Chen Y, Wang H, Liang M,Zou R, Tang Z, Wang J. Upregulation of miR-3658 in bladder cancer and tumor progression. Genet Mol Res 2016;21:2274–82.
33. Hao M, Zang M, Wendlandt E, Xu Y, An G, Gong D, et al. Low serum mi R‐19a expression as a novel poor prognostic indica- tor in multiple myeloma. IntJ Cancer 2015;136(8):1835–44.
34. Kong Q, Han J, Deng H, Wu F, Guo S, Ye Z. miR-431-5p alters the epithelial-to-mesenchymal transition markers by tar- geting UROC28 in hepatoma cells. OncoTargets Therapy 2018;11:6489.
35. MengY, Quan L, Liu A. Identification of key microRNAs associ- ated with diffuse large B-cell lymphoma by analyzing serum microRNA expressions. Gene 2018;642:205–11.
36. Yang Z, Wei Z, Wu X, Yang H. Screening of exosomal miRNAs derived from subcutaneous and visceral adipose tissues: De- termination of targets for the treatment of obesity and associ- ated metabolic disorders. Mol Med Rep 2018;18(3):3314–24.
37. Son GW, Yang H, Park HR, Lee SE, Jin YH, Park CS, et al. Analysis of miRNA expression profiling in melatonin-exposuredendo- thelial cells. Mol Cell Toxicol 2016;12(1):73–81.
38. Lorusso C, De Summa S, Pinto R, Danza K, Tommasi S. miRNAs as key players in the management of cutaneous melanoma. Cells 2020;9(2):415.
39. Li Z, Yang H, Ye L, Quan R, Chen M. Role of exosomal miRNAs in brain metastasis affected by radiotherapy. Trans Neurosci 2021;12(1):127–37.
40. Tao L, Zeng Y, Wang J, Liu Z, Shen B, Ge J, et al. Differential microRNA expression in aristolochic acid-induced upper uro- thelial tract cancers ex vivo. Mol Med Rep 2015;12(5):6533–46.
41. Bara Jr T, Gurzu S, Sugimura H, Bara T, Beleaua MA, Jung I. A systematic review of the possible carcinogenic role of the aris- tolochic acid. Rom J Morphol Embryol 2017;58(1):41–4.