Diagnostic and therapeutic role of microRNAs in oral cancer (Review)

Wang,Jing; Lv,Najun; Lu,Xinxin; Yuan,Rongtao; Chen,Zhenggang; Yu,Jiangbo

doi:10.3892/or.2020.7854

Diagnostic and therapeutic role of microRNAs in oral cancer (Review)

Authors:
- Jing Wang
- Najun Lv
- Xinxin Lu
- Rongtao Yuan
- Zhenggang Chen
- Jiangbo Yu
View Affiliations

Affiliations: Oral Research Center, Qingdao Municipal Hospital, Qingdao, Shandong 266011, P.R. China
Published online on: November 13, 2020 https://doi.org/10.3892/or.2020.7854
Pages: 58-64
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Oral cancer is one of the leading types of cancer and remains the most common cause of cancer‑related mortality in Asia. The pathogenesis of oral cancer is complicated and, due to lack of accurate diagnostic methods and efficient treatment strategies, oral cancer is responsible for a large number of deaths. Therefore, there is an urgent need for developing novel diagnostic tools and targeted therapies. MicroRNAs (miRNAs) represent a class of small non‑coding RNAs that are key elements and play critical regulatory roles in the pathological processes of various diseases. miRNAs are widely distributed in body fluids and are specifically expressed in different cancers, and they may represent effective biomarkers that may be used for early detection of oral cancer. In addition, miRNAs are involved in oral cancer development, progression and prognosis by targeting a broad range of mRNAs that may be of therapeutic value for oral cancer. The aim of the present review was to summarize the role of miRNAs as new diagnostic tools and potential therapeutic targets in oral cancer, and investigate the underlying molecular mechanisms.

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1	Santoro A, Pannone G, Papagerakis S, Serpico R and Bufo P: Epigenetic profiling of oral cancer. InTech. Mar 14–2012.(Epub ahead of print). doi: 10.5772/31386.
2	Tsantoulis PK, Kastrinakis NG, Tourvas AD, Laskaris G and Gorgoulis VG: Advances in the biology of oral cancer. Oral Oncol. 43:523–534. 2007. View Article : Google Scholar
3	Gupta B, Johnson NW and Kumar N: Global epidemiology of head and neck cancers: A continuing challenge. Oncology. 91:13–23. 2016. View Article : Google Scholar
4	Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA and Jemal A: Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 68:394–424. 2018. View Article : Google Scholar
5	Huppi K, Volfovsky N, Mackiewicz M, Runfola T, Jones TL, Martin SE, Stephens R and Caplen NJ: MicroRNAs and genomic instability. Semin Cancer Biol. 17:65–73. 2007. View Article : Google Scholar
6	Mitchell PS, Parkin RK, Kroh EM, Fritz BR, Wyman SK, Pogosova-Agadjanyan EL, Peterson A, Noteboom J, O'Briant KC, Allen A, et al: Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci USA. 105:10513–10518. 2008. View Article : Google Scholar
7	Chawla JP, Iyer N, Soodan KS, Sharma A, Khurana SK and Priyadarshni P: Role of miRNA in cancer diagnosis, prognosis, therapy and regulation of its expression by Epstein-Barr virus and human papillomaviruses: With special reference to oral cancer. Oral Oncol. 51:731–737. 2015. View Article : Google Scholar
8	Chen X, Ba Y, Ma L, Cai X, Yin Y, Wang K, Guo J, Zhang Y, Chen J, Guo X, et al: Characterization of microRNAs in serum: A novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res. 18:997–1006. 2008. View Article : Google Scholar
9	Croce CM and Calin GA: miRNAs, cancer, and stem cell division. Cell. 122:6–7. 2005. View Article : Google Scholar
10	Di Leva G, Garofalo M and Croce CM: MicroRNAs in cancer. Annu Rev Pathol. 9:287–314. 2014. View Article : Google Scholar
11	Fabbri M: MicroRNAs and cancer: Towards a personalized medicine. Curr Mol Med. 13:751–756. 2013. View Article : Google Scholar
12	Madhura MG, Rao RS, Patil S, Fageeh HN, Alhazmi A and Awan KH: Advanced diagnostic aids for oral cancer. Dis Mon. Jun 25–2020.(Epub ahead of print). doi: 10.1016/j.disamonth.2020.101034. View Article : Google Scholar
13	Gombos K, Horváth R, Szele E, Juhász K, Gocze K, Somlai K, Pajkos G, Ember I and Olasz L: miRNA expression profiles of oral squamous cell carcinomas. Anticancer Res. 33:1511–1517. 2013.
14	Maclellan SA, Lawson J, Baik J, Guillaud M, Poh CF and Garnis C: Differential expression of miRNAs in the serum of patients with high-risk oral lesions. Cancer Med. 1:268–274. 2012. View Article : Google Scholar
15	Momen-Heravi F, Trachtenberg AJ, Kuo WP and Cheng YS: Genomewide study of salivary MicroRNAs for detection of oral cancer. J Dent Res. 93 (Suppl 7):86S–93S. 2014. View Article : Google Scholar
16	He Q, Chen Z, Cabay RJ, Zhang L, Luan X, Chen D, Yu T, Wang A and Zhou X: microRNA-21 and microRNA-375 from oral cytology as biomarkers for oral tongue cancer detection. Oral Oncol. 57:15–20. 2016. View Article : Google Scholar
17	Chen L, Hu J, Pan L, Yin X, Wang Q and Chen H: Diagnostic and prognostic value of serum miR-99a expression in oral squamous cell carcinoma. Cancer Biomark. 23:333–339. 2018. View Article : Google Scholar
18	He L, Ping F, Fan Z, Zhang C, Deng M, Cheng B and Xia J: Salivary exosomal miR-24-3p serves as a potential detective biomarker for oral squamous cell carcinoma screening. Biomed Pharmacother. 121:1095532020. View Article : Google Scholar
19	Lu Z, He Q, Liang J, Li W, Su Q, Chen Z, Wan Q, Zhou X, Cao L, Sun J, et al: miR-31-5p is a potential circulating biomarker and therapeutic target for oral cancer. Mol Ther Nucleic Acids. 16:471–480. 2019. View Article : Google Scholar
20	Gai C, Camussi F, Broccoletti R, Gambino A, Cabras M, Molinaro L, Carossa S, Camussi G and Arduino PG: Salivary extracellular vesicle-associated miRNAs as potential biomarkers in oral squamous cell carcinoma. BMC Cancer. 18:4392018. View Article : Google Scholar
21	Chang YA, Weng SL, Yang SF, Chou CH, Huang WC, Tu SJ, Chang TH, Huang CN, Jong YJ and Huang HD: A Three-MicroRNA signature as a potential biomarker for the early detection of oral cancer. Int J Mol Sci. 19:7582018. View Article : Google Scholar
22	Berania I, Cardin GB, Clément I, Guertin L, Ayad T, Bissada E, Nguyen-Tan PF, Filion E, Guilmette J, Gologan O, et al: Four PTEN-targeting co-expressed miRNAs and ACTN4-targeting miR-548b are independent prognostic biomarkers in human squamous cell carcinoma of the oral tongue. Int J Cancer. 141:2318–2328. 2017. View Article : Google Scholar
23	Supic G, Zeljic K, Rankov AD, Kozomara R, Nikolic A, Radojkovic D and Magic Z: miR-183 and miR-21 expression as biomarkers of progression and survival in tongue carcinoma patients. Clin Oral Investig. 22:401–409. 2018. View Article : Google Scholar
24	Xu H, Yang Y, Zhao H, Yang X, Luo Y, Ren Y, Liu W and Li N: Serum miR-483-5p: A novel diagnostic and prognostic biomarker for patients with oral squamous cell carcinoma. Tumour Biol. 37:447–453. 2016. View Article : Google Scholar
25	Gu WL, Ye DX and Wu JJ: Expression and clinical significance of plasma microRNA-125b level in patients with oral squamous cell carcinoma. Shanghai Kou Qiang Yi Xue. 24:71–75. 2015.(In Chinese).
26	Zahran F, Ghalwash D, Shaker O, Al-Johani K and Scully C: Salivary microRNAs in oral cancer. Oral Dis. 21:739–747. 2015. View Article : Google Scholar
27	Lu YC, Chang JT, Huang YC, Huang CC, Chen WH, Lee LY, Huang BS, Chen YJ, Li HF and Cheng AJ: Combined determination of circulating miR-196a and miR-196b levels produces high sensitivity and specificity for early detection of oral cancer. Clin Biochem. 48:115–121. 2015. View Article : Google Scholar
28	Ries J, Vairaktaris E, Kintopp R, Baran C, Neukam FW and Nkenke E: Alterations in miRNA expression patterns in whole blood of OSCC patients. In Vivo. 28:851–861. 2014.
29	Ries J, Baran C, Wehrhan F, Weber M, Motel C, Kesting M and Nkenke E: The altered expression levels of miR-186, miR-494 and miR-3651 in OSCC tissue vary from those of the whole blood of OSCC patients. Cancer Biomark. 24:19–30. 2019. View Article : Google Scholar
30	Wu N, Lu Y and Liang JZ: Expression and correlation of survivin and hsa-miR-542-3p in patients with oral squamous cell carcinoma. Shanghai Kou Qiang Yi Xue. 25:720–724. 2016.(In Chinese).
31	Duz MB, Karatas OF, Guzel E, Turgut NF, Yilmaz M, Creighton CJ and Ozen M: Identification of miR-139-5p as a saliva biomarker for tongue squamous cell carcinoma: A pilot study. Cell Oncol (Dordr). 39:187–193. 2016. View Article : Google Scholar
32	Lai YH, Liu H, Chiang WF, Chen TW, Chu LJ, Yu JS, Chen SJ, Chen HC and Tan BC: MiR-31-5p-ACOX1 Axis enhances tumorigenic fitness in oral squamous cell carcinoma via the promigratory prostaglandin E2. Theranostics. 8:486–504. 2018. View Article : Google Scholar
33	Zheng X, Wu K, Liao S, Pan Y, Sun Y, Chen X, Zhang Y, Xia S, Hu Y and Zhang J: MicroRNA-transcription factor network analysis reveals miRNAs cooperatively suppress RORA in oral squamous cell carcinoma. Oncogenesis. 7:792018. View Article : Google Scholar
34	Cheng CM, Shiah SG, Huang CC, Hsiao JR and Chang JY: Up-regulation of miR-455-5p by the TGF-β-SMAD signalling axis promotes the proliferation of oral squamous cancer cells by targeting UBE2B. J Pathol. 240:38–49. 2016. View Article : Google Scholar
35	Agarwal V, Bell GW, Nam JW and Bartel DP: Predicting effective microRNA target sites in mammalian mRNAs. Elife. 4:e050052015. View Article : Google Scholar
36	Wu M, Duan Q, Liu X, Zhang P, Fu Y, Zhang Z, Liu L, Cheng J and Jiang H: MiR-155-5p promotes oral cancer progression by targeting chromatin remodeling gene ARID2. Biomed Pharmacother. 122:1096962020. View Article : Google Scholar
37	Chen YH, Song Y, Yu YL, Cheng W and Tong X: miRNA-10a promotes cancer cell proliferation in oral squamous cell carcinoma by upregulating GLUT1 and promoting glucose metabolism. Oncol Lett. 17:5441–5446. 2019.
38	Higaki M, Shintani T, Hamada A, Rosli SNZ and Okamoto T: Eldecalcitol (ED-71)-induced exosomal miR-6887-5p suppresses squamous cell carcinoma cell growth by targeting heparin-binding protein 17/fibroblast growth factor-binding protein-1 (HBp17/FGFBP-1). In vitro cellular & developmental biology. In Vitro Cell Dev Biol Anim. 56:222–233. 2020. View Article : Google Scholar
39	Li YY, Tao YW, Gao S, Li P, Zheng JM, Zhang SE, Liang J and Zhang Y: Cancer-associated fibroblasts contribute to oral cancer cells proliferation and metastasis via exosome-mediated paracrine miR-34a-5p. EBioMedicine. 36:209–220. 2018. View Article : Google Scholar
40	Dickman CT, Lawson J, Jabalee J, MacLellan SA, LePard NE, Bennewith KL and Garnis C: Selective extracellular vesicle exclusion of miR-142-3p by oral cancer cells promotes both internal and extracellular malignant phenotypes. Oncotarget. 8:15252–15266. 2017. View Article : Google Scholar
41	Fang X, Tang Z, Zhang H and Quan H: Long non-coding RNA DNM3OS/miR-204-5p/HIP1 axis modulates oral cancer cell viability and migration. J Oral Pathol Med. 49:865–875. 2020. View Article : Google Scholar
42	Jakob M, Mattes LM, Küffer S, Unger K, Hess J, Bertlich M, Haubner F, Ihler F, Canis M, Weiss BG and Kitz J: MicroRNA expression patterns in oral squamous cell carcinoma: hsa-mir-99b-3p and hsa-mir-100-5p as novel prognostic markers for oral cancer. Head Neck. 41:3499–3515. 2019. View Article : Google Scholar
43	Falzone L, Lupo G, La Rosa GR, Crimi S, Anfuso CD, Salemi R, Rapisarda E, Libra M and Candido S: Identification of Novel MicroRNAs and their diagnostic and prognostic significance in oral cancer. Cancers. 11:6102019. View Article : Google Scholar
44	Hsing EW, Shiah SG, Peng HY, Chen YW, Chuu CP, Hsiao JR, Lyu PC and Chang JY: TNF-α-induced miR-450a mediates TMEM182 expression to promote oral squamous cell carcinoma motility. PLoS One. 14:e02134632019. View Article : Google Scholar
45	Kurihara-Shimomura M, Sasahira T, Shimomura H, Nakashima C and Kirita T: miR-29b-1-5p the oncogenic activity of induces the epithelial-mesenchymal transition in oral squamous cell carcinoma. J Clin Med. 24:2732019. View Article : Google Scholar
46	Lu Y, Li Y, Wang Z, Xie S, Wang Q, Lei X, Ruan Y and Li J: Downregulation of RGMA by HIF-1A/miR-210-3p axis promotes cell proliferation in oral squamous cell carcinoma. Biomed Pharmacother. 112:1086082019. View Article : Google Scholar
47	Yuan G, Wu H, Du Y and He F: Tumor suppressor role of microRNA-545 in oral squamous cell carcinoma. Oncol Lett. 17:2063–2068. 2019.
48	Qiu YF, Wang MX, Meng LN, Zhang R and Wang W: MiR-21 regulates proliferation and apoptosis of oral cancer cells through TNF-α. Eur Rev Med Pharmacol Sci. 22:7735–7741. 2018.
49	Zheng J, Wang J, Jia Y, Liu T, Duan Y, Liang X and Liu L: microRNA-211 promotes proliferation, migration, and invasion ability of oral squamous cell carcinoma cells via targeting the bridging integrator 1 protein. J Cell Biochem. 120:4644–4653. 2019. View Article : Google Scholar
50	Peng SY, Tu HF, Yang CC, Wu CH, Liu CJ, Chang KW and Lin SC: miR-134 targets PDCD7 to reduce E-cadherin expression and enhance oral cancer progression. Int J Cancer. 143:2892–2904. 2018. View Article : Google Scholar
51	Kim JS, Choi DW, Kim CS, Yu SK, Kim HJ, Go DS, Lee SA, Moon SM, Kim SG, Chun HS, et al: MicroRNA-203 induces apoptosis by targeting in YD-38 oral cancer cells. Anticancer Res. 38:3477–3485. 2018. View Article : Google Scholar
52	Wang L, Wei Y, Yan Y, Wang H, Yang J, Zheng Z, Zha J, Bo P, Tang Y, Guo X, et al: CircDOCK1 suppresses cell apoptosis via inhibition of miR-196a-5p by targeting BIRC3 in OSCC. Oncol Rep. 39:951–966. 2018.
53	Ruan P, Tao Z and Tan A: Low expression of miR-30a-5p induced the proliferation and invasion of oral cancer via promoting the expression of FAP. Biosci Rep. 38:BSR201710272018. View Article : Google Scholar
54	Sakha S, Muramatsu T, Ueda K and Inazawa J: Exosomal microRNA miR-1246 induces cell motility and invasion through the regulation of DENND2D in oral squamous cell carcinoma. Sci Rep. 6:387502016. View Article : Google Scholar
55	Chuerduangphui J, Ekalaksananan T, Chaiyarit P, Patarapadungkit N, Chotiyano A, Kongyingyoes B, Promthet S and Pientong C: Effects of arecoline on proliferation of oral squamous cell carcinoma cells by dysregulating c-Myc and miR-22, directly targeting oncostatin M. PLoS One. 13:e01920092018. View Article : Google Scholar
56	Harsha C, Banik K, Ang HL, Girisa S, Vikkurthi R, Parama D, Rana V, Shabnam B, Khatoon E, Kumar AP and Kunnumakkara AB: Targeting AKT/mTOR in oral cancer: Mechanisms and advances in clinical trials. Int J Mol Sci. 21:32852020. View Article : Google Scholar
57	Manikandan M, Deva Magendhra Rao AK, Arunkumar G, Manickavasagam M, Rajkumar KS, Rajaraman R and Munirajan AK: Oral squamous cell carcinoma: microRNA expression profiling and integrative analyses for elucidation of tumourigenesis mechanism. Mol Cancer. 15:282016. View Article : Google Scholar
58	Uesugi A, Kozaki K, Tsuruta T, Furuta M, Morita K, Imoto I, Omura K and Inazawa J: The tumor suppressive microRNA miR-218 targets the mTOR component Rictor and inhibits AKT phosphorylation in oral cancer. Cancer Res. 71:5765–5778. 2011. View Article : Google Scholar
59	Moratin J, Hartmann S, Brands R, Brisam M, Mutzbauer G, Scholz C, Seher A, Müller-Richter U, Kübler AC and Linz C: Evaluation of miRNA-expression and clinical tumour parameters in oral squamous cell carcinoma (OSCC). J Craniomaxillofac Surg. 44:876–881. 2016. View Article : Google Scholar
60	Chen D, Chen Z, Jin Y, Dragas D, Zhang L, Adjei BS, Wang A, Dai Y and Zhou X: MicroRNA-99 family members suppress Homeobox A1 expression in epithelial cells. PLoS One. 8:e806252013. View Article : Google Scholar
61	Chen R, Zhang Y and Zhang X: MiR-1254 functions as a tumor suppressor in oral squamous cell carcinoma by targeting CD36. Technol Cancer Res Treat. Aug 11–2019.doi: 10.1177/1533033819859447. View Article : Google Scholar
62	Chen X, Xu H, Sun G and Zhang Y: LncRNA CASC9 affects cell proliferation, migration, and invasion of tongue squamous cell carcinoma via regulating miR-423-5p/SOX12 Axes. Cancer Manage Res. 12:277–287. 2020. View Article : Google Scholar
63	Rastogi B, Kumar A, Raut SK, Panda NK, Rattan V, Joshi N and Khullar M: Downregulation of miR-377 promotes oral squamous cell carcinoma growth and migration by targeting HDAC9. Cancer Invest. 35:152–162. 2017. View Article : Google Scholar
64	Chen F, Qi S, Zhang X, Wu J, Yang X and Wang R: miR-23a-3p suppresses cell proliferation in oral squamous cell carcinomas by targeting FGF2 and correlates with a better prognosis: miR-23a-3p inhibits OSCC growth by targeting FGF2. Pathol Res Pract. 215:660–667. 2019. View Article : Google Scholar
65	Li X, Liu K, Zhou W and Jiang Z: MiR-155 targeting FoxO3a regulates oral cancer cell proliferation, apoptosis, and DDP resistance through targeting FoxO3a. Cancer Biomark. 27:105–111. 2020. View Article : Google Scholar
66	Fu S, Chen HH, Cheng P, Zhang CB and Wu Y: MiR-155 regulates oral squamous cell carcinoma Tca8113 cell proliferation, cycle, and apoptosis via regulating p27Kip1. Eur Rev Med Pharmacol Sci. 21:937–944. 2017.
67	Bufalino A, Cervigne NK, de Oliveira CE, Fonseca FP, Rodrigues PC, Macedo CC, Sobral LM, Miguel MC, Lopes MA, Paes Leme AF, et al: Low miR-143/miR-145 cluster levels induce activin A overexpression in oral squamous cell carcinomas, which contributes to poor prognosis. PLoS One. 10:e01365992015. View Article : Google Scholar
68	Huang WC, Chan SH, Jang TH, Chang JW, Ko YC, Yen TC, Chiang SL, Chiang WF, Shieh TY, Liao CT, et al: miRNA-491-5p and GIT1 serve as modulators and biomarkers for oral squamous cell carcinoma invasion and metastasis. Cancer Res. 74:751–764. 2014. View Article : Google Scholar
69	Yu EH, Tu HF, Wu CH, Yang CC and Chang KW: MicroRNA-21 promotes perineural invasion and impacts survival in patients with oral carcinoma. J Chin Med Assoc. 80:383–388. 2017. View Article : Google Scholar
70	Tu HF, Chang KW, Cheng HW and Liu CJ: Upregulation of miR-372 and −373 associates with lymph node metastasis and poor prognosis of oral carcinomas. Laryngoscope. 125:E365–E370. 2015. View Article : Google Scholar
71	Zhang B, Li Y, Hou D, Shi Q, Yang S and Li Q: MicroRNA-375 inhibits growth and enhances radiosensitivity in oral squamous cell carcinoma by targeting insulin like growth factor 1 receptor. Cell Physiol Biochem. 42:2105–2117. 2017. View Article : Google Scholar
72	Weng JH, Yu CC, Lee YC, Lin CW, Chang WW and Kuo YL: miR-494-3p induces cellular senescence and enhances radiosensitivity in human oral squamous carcinoma cells. Int J Mol Sci. 17:10922016. View Article : Google Scholar
73	Min A, Zhu C, Peng S, Shuai C, Sun L, Han Y, Qian Y, Gao S and Su T: Downregulation of Microrna-148a in cancer-associated fibroblasts from oral cancer promotes cancer cell migration and invasion by targeting Wnt10b. J Biochem Mol Toxicol. 30:186–191. 2016. View Article : Google Scholar