Expression and promoter methylation of Wnt inhibitory factor-1 in the development of oral submucous fibrosis

Zhou,Shanghui; Chen,Ling; Mashrah,Mubarak; Zhu,Yun; He,Zhijing; Hu,Yuhua; Xiang,Tingxiu; Yao,Zhigang; Guo,Feng; Zhang,Chenping

doi:10.3892/or.2015.4264

Expression and promoter methylation of Wnt inhibitory factor-1 in the development of oral submucous fibrosis

Authors:
- Shanghui Zhou
- Ling Chen
- Mubarak Mashrah
- Yun Zhu
- Zhijing He
- Yuhua Hu
- Tingxiu Xiang
- Zhigang Yao
- Feng Guo
- Chenping Zhang
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Affiliations: Department of Oral and Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200011, P.R. China, Molecular Oncology and Epigenetics Laboratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China, Department of Oral and Maxillofacial Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China, Department of Oral Pathology, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200011, P.R. China, Department of Oral Pathology, Xiangya Stomatological Hospital, Central South University, Changsha, Hunan 410078, P.R. China, Department of Oral and Maxillofacial Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China
Published online on: September 9, 2015 https://doi.org/10.3892/or.2015.4264
Pages: 2636-2642

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Abstract

Oral squamous cell carcinoma (OSCC) is a type of head and neck malignancy with a high mortality rate. Oral submucous fibrosis (OSF) is the pre-cancerous lesion of OSCC, whose molecular mechanisms in OSCC tumorigenesis remain largely unclear. Activation of the Wnt/β-catenin signaling pathway plays an important role in oral mucous carcinogenesis, although rare mutations of Wnt signaling molecules are found in OSCC, suggesting an epigenetic mechanism mediating aberrant Wnt/β‑catenin signaling in OSCC. Wnt inhibitory factor-1 (WIF1) is an Wnt antagonist, and its downregulation and methylation have been reported in a number of malignancies. However, the expression and methylation of WIF1 in the development of OSF have yet to be reported. In the present study, we investigated the WIF1 expression level by immunohistochemical staining and semi‑quantitative RT-PCR in normal oral, OSF and OSCC tissues, as well as the methylation status by methylation-specific PCR and bisulfite genomic sequencing. The results showed that WIF1 was readily expressed in normal oral mucous tissues, but decreased gradually in OSF early, moderately advanced and advanced tissues, and was less expressed in OSCC tissues. Moreover, WIF1 was able to translocate from the nuclear to cytoplasm in OSF and OSCC tissues. Furthermore, WIF1 was frequently methylated in OSCC cases with betel quid chewing habit, but not in normal oral mucous and different stages of OSF tissues, suggesting WIF1 methylation is tumor-specific in the development of OSF. Thus, the results demonstrated that WIF1 is frequently downregulated or silenced by promoter methylation in the carcinogenesis of OSF, which serves as a potential epigenetic biomarker for the early detection of OSCC.

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1	Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J and Jemal A: Global cancer statistics, 2012. CA Cancer J Clin. 65:87–108. 2015. View Article : Google Scholar : PubMed/NCBI
2	Braakhuis BJ, Brakenhoff RH and Leemans CR: Head and neck cancer: Molecular carcinogenesis. Ann Oncol. 16(Suppl 2): ii249–ii250. 2005. View Article : Google Scholar : PubMed/NCBI
3	Leemans CR, Braakhuis BJ and Brakenhoff RH: The molecular biology of head and neck cancer. Nat Rev Cancer. 11:9–22. 2011. View Article : Google Scholar
4	Choi S and Myers JN: Molecular pathogenesis of oral squamous cell carcinoma: Implications for therapy. J Dent Res. 87:14–32. 2008. View Article : Google Scholar
5	Pindborg JJ, Murti PR, Bhonsle RB, Gupta PC, Daftary DK and Mehta FS: Oral submucous fibrosis as a precancerous condition. Scand J Dent Res. 92:224–229. 1984.PubMed/NCBI
6	Pindborg JJ and Sirsat SM: Oral submucous fibrosis. Oral Surg Oral Med Oral Pathol. 22:764–779. 1966. View Article : Google Scholar : PubMed/NCBI
7	Tilakaratne WM, Klinikowski MF, Saku T, Peters TJ and Warnakulasuriya S: Oral submucous fibrosis: Review on aetiology and pathogenesis. Oral Oncol. 42:561–568. 2006. View Article : Google Scholar
8	Wollina U, Verma SB, Ali FM and Patil K: Oral submucous fibrosis: An update. Clin Cosmet Investig Dermatol. 8:193–204. 2015. View Article : Google Scholar : PubMed/NCBI
9	Murti PR, Bhonsle RB, Pindborg JJ, Daftary DK, Gupta PC and Mehta FS: Malignant transformation rate in oral submucous fibrosis over a 17-year period. Community Dent Oral Epidemiol. 13:340–341. 1985. View Article : Google Scholar : PubMed/NCBI
10	Zhang X and Reichart PA: A review of betel quid chewing, oral cancer and precancer in Mainland China. Oral Oncol. 43:424–430. 2007. View Article : Google Scholar : PubMed/NCBI
11	Pillai R, Balaram P and Reddiar KS: Pathogenesis of oral submucous fibrosis. Relationship to risk factors associated with oral cancer. Cancer. 69:2011–2020. 1992. View Article : Google Scholar : PubMed/NCBI
12	Jian XC, Liu SF, Shen ZH and Yang YH: Histomorphology of oral submucous fibrosis. Report of 24 cases. Chin Med J (Engl). 101:505–509. 1988.
13	Jones PA and Baylin SB: The fundamental role of epigenetic events in cancer. Nat Rev Genet. 3:415–428. 2002.PubMed/NCBI
14	Jones PA and Baylin SB: The epigenomics of cancer. Cell. 128:683–692. 2007. View Article : Google Scholar : PubMed/NCBI
15	Baylin SB and Jones PA: A decade of exploring the cancer epigenome - biological and translational implications. Nat Rev Cancer. 11:726–734. 2011. View Article : Google Scholar : PubMed/NCBI
16	Supić G, Kozomara R, Branković-Magić M, Jović N and Magić Z: Gene hypermethylation in tumor tissue of advanced oral squamous cell carcinoma patients. Oral Oncol. 45:1051–1057. 2009. View Article : Google Scholar
17	Towle R, Truong D, Hogg K, Robinson WP, Poh CF and Garnis C: Global analysis of DNA methylation changes during progression of oral cancer. Oral Oncol. 49:1033–1042. 2013. View Article : Google Scholar : PubMed/NCBI
18	Pannone G, Bufo P, Santoro A, Franco R, Aquino G, Longo F, Botti G, Serpico R, Cafarelli B, Abbruzzese A, et al: WNT pathway in oral cancer: Epigenetic inactivation of WNT-inhibitors. Oncol Rep. 24:1035–1041. 2010.PubMed/NCBI
19	Ha PK and Califano JA: Promoter methylation and inactivation of tumour-suppressor genes in oral squamous-cell carcinoma. Lancet Oncol. 7:77–82. 2006. View Article : Google Scholar : PubMed/NCBI
20	Liu F and Millar SE: Wnt/beta-catenin signaling in oral tissue development and disease. J Dent Res. 89:318–330. 2010. View Article : Google Scholar : PubMed/NCBI
21	Noguti J, DE Moura CF, Hossaka TA, Franco M, Oshima CT, Dedivitis RA and Ribeiro DA: The role of canonical WNT signaling pathway in oral carcinogenesis: A comprehensive review. Anticancer Res. 32:873–878. 2012.PubMed/NCBI
22	Hsieh JC, Kodjabachian L, Rebbert ML, Rattner A, Smallwood PM, Samos CH, Nusse R, Dawid IB and Nathans J: A new secreted protein that binds to Wnt proteins and inhibits their activities. Nature. 398:431–436. 1999. View Article : Google Scholar : PubMed/NCBI
23	Gupta PC, Sinor PN, Bhonsle RB, Pawar VS and Mehta HC: Oral submucous fibrosis in India: A new epidemic? Natl Med J India. 11:113–116. 1998.PubMed/NCBI
24	Chan SL, Cui Y, van Hasselt A, Li H, Srivastava G, Jin H, Ng KM, Wang Y, Lee KY, Tsao GS, et al: The tumor suppressor Wnt inhibitory factor 1 is frequently methylated in nasopharyngeal and esophageal carcinomas. Lab Invest. 87:644–650. 2007. View Article : Google Scholar : PubMed/NCBI
25	Ai L, Tao Q, Zhong S, Fields CR, Kim WJ, Lee MW, Cui Y, Brown KD and Robertson KD: Inactivation of Wnt inhibitory factor-1 (WIF1) expression by epigenetic silencing is a common event in breast cancer. Carcinogenesis. 27:1341–1348. 2006. View Article : Google Scholar : PubMed/NCBI
26	Qiu GH, Tan LK, Loh KS, Lim CY, Srivastava G, Tsai ST, Tsao SW and Tao Q: The candidate tumor suppressor gene BLU, located at the commonly deleted region 3p21.3, is an E2F-regulated, stress-responsive gene and inactivated by both epigenetic and genetic mechanisms in nasopharyngeal carcinoma. Oncogene. 23:4793–4806. 2004. View Article : Google Scholar : PubMed/NCBI
27	Ying J, Li H, Seng TJ, Langford C, Srivastava G, Tsao SW, Putti T, Murray P, Chan AT and Tao Q: Functional epigenetics identifies a protocadherin PCDH10 as a candidate tumor suppressor for nasopharyngeal, esophageal and multiple other carcinomas with frequent methylation. Oncogene. 25:1070–1080. 2006. View Article : Google Scholar
28	Anastas JN and Moon RT: WNT signalling pathways as therapeutic targets in cancer. Nat Rev Cancer. 13:11–26. 2013. View Article : Google Scholar
29	Clevers H: Wnt/beta-catenin signaling in development and disease. Cell. 127:469–480. 2006. View Article : Google Scholar : PubMed/NCBI
30	Polakis P: The many ways of Wnt in cancer. Curr Opin Genet Dev. 17:45–51. 2007. View Article : Google Scholar : PubMed/NCBI
31	Iwai S, Katagiri W, Kong C, Amekawa S, Nakazawa M and Yura Y: Mutations of the APC, beta-catenin, and axin 1 genes and cytoplasmic accumulation of beta-catenin in oral squamous cell carcinoma. J Cancer Res Clin Oncol. 131:773–782. 2005. View Article : Google Scholar : PubMed/NCBI
32	Ding Z, Qian YB, Zhu LX and Xiong QR: Promoter methylation and mRNA expression of DKK-3 and WIF-1 in hepatocellular carcinoma. World J Gastroenterol. 15:2595–2601. 2009. View Article : Google Scholar : PubMed/NCBI
33	Lin YC, You L, Xu Z, He B, Mikami I, Thung E, Chou J, Kuchenbecker K, Kim J, Raz D, et al: Wnt signaling activation and WIF-1 silencing in nasopharyngeal cancer cell lines. Biochem Biophys Res Commun. 341:635–640. 2006. View Article : Google Scholar : PubMed/NCBI
34	Yee DS, Tang Y, Li X, Liu Z, Guo Y, Ghaffar S, McQueen P, Atreya D, Xie J, Simoneau AR, et al: The Wnt inhibitory factor 1 restoration in prostate cancer cells was associated with reduced tumor growth, decreased capacity of cell migration and invasion and a reversal of epithelial to mesenchymal transition. Mol Cancer. 9:1622010. View Article : Google Scholar : PubMed/NCBI
35	Mazieres J, He B, You L, Xu Z, Lee AY, Mikami I, Reguart N, Rosell R, McCormick F and Jablons DM: Wnt inhibitory factor-1 is silenced by promoter hypermethylation in human lung cancer. Cancer Res. 64:4717–4720. 2004. View Article : Google Scholar : PubMed/NCBI
36	Taniguchi H, Yamamoto H, Hirata T, Miyamoto N, Oki M, Nosho K, Adachi Y, Endo T, Imai K and Shinomura Y: Frequent epigenetic inactivation of Wnt inhibitory factor-1 in human gastrointestinal cancers. Oncogene. 24:7946–7952. 2005. View Article : Google Scholar : PubMed/NCBI
37	Paluszczak J, Sarbak J, Kostrzewska-Poczekaj M, Kiwerska K, Jarmuż-Szymczak M, Grenman R, Mielcarek-Kuchta D and Baer-Dubowska W: The negative regulators of Wnt pathway-DACH1, DKK1, and WIF1 are methylated in oral and oropharyngeal cancer and WIF1 methylation predicts shorter survival. Tumour Biol. 36:2855–2861. 2015. View Article : Google Scholar