Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 3/2013

01-12-2013 | Translational Research and Biomarkers

miR-196a Overexpression and miR-196a2 Gene Polymorphism Are Prognostic Predictors of Oral Carcinomas

Authors: Chung-Ji Liu, DDS, MS, Meng-Miao Tsai, PhD, Hsi-Feng Tu, DDS, PhD, Man-Tin Lui, DDS, Hui-Wen Cheng, MS, Shu-Chun Lin, PhD

Published in: Annals of Surgical Oncology | Special Issue 3/2013

Login to get access

Abstract

Background

Oral squamous cell carcinoma (OSCC) is prevalent worldwide, and survival in OSCC has not improved significantly in the last few decades. MicroRNAs have an important regulatory role in oral carcinogenesis. This study investigated the prognostic implications of miR-196 expression and the rs11614913 genotype of the miR-196a2 gene in OSCC.

Methods

The clinicopathologic implications of miR-196 in OSCC were investigated using expression assays and genotyping, and the functional role of miR-196 in OSCC pathogenesis was investigated using exogenous expression and knockdown.

Results

miR-196 was up-regulated in OSCC tissue relative to control mucosa. High expression of miR-196a, but not miR-196b, was associated with tumor recurrence, nodal metastasis, and mortality. Plasma miR-196a levels could be used to distinguish patients from controls with a separating power of 0.75. Multivariate analysis showed that both high miR-196a expression and TT genotype were independent predictors for poor survival in OSCC. The risk of mortality was greatest for patients with high miR-196a level and positive node status. Expression of miR-196 enhanced oncogenesis of OSCC cells, while inhibition of miR-196 expression attenuated such effects.

Conclusions

High miR-196a expression in tumor tissue and the presence of the TT variant of miR-196a2 gene indicate worse survival in OSCC.
Appendix
Available only for authorised users
Literature
1.
Liu CJ, Tsai MM, Hung PS, Kao SY, Liu TY, Wu KJ, et al. miR-31 ablates expression of the HIF regulatory factor FIH to activate the HIF pathway in head and neck carcinoma. Cancer Res. 2010;70:1635–44.CrossRefPubMed
2.
Shieh TM, Lin SC, Liu CJ, Chang SS, Ku TH, Chang KW. Association of expression aberrances and genetic polymorphisms of lysyl oxidase with areca-associated oral tumorigenesis. Clin Cancer Res. 2007;13:4378–85.CrossRefPubMed
3.
Chen YJ, Lin SC, Kao T, Chang CS, Hong PS, Shieh TM, et al. Genome-wide profiling of oral squamous cell carcinoma. J Pathol. 2004;204:326–32.CrossRefPubMed
4.
Braakhuis BJ, Tabor MP, Leemans CR, van der Waal I, Snow GB, Brakenhoff RH. Second primary tumors and field cancerization in oral and oropharyngeal cancer: molecular techniques provide new insights and definitions. Head Neck. 2002;24:198–206.CrossRefPubMed
5.
Liu CJ, Liu TY, Kuo LT, Cheng HW, Chu TH, Chang KW, et al. Differential gene expression signature between primary and metastatic head and neck squamous cell carcinoma. J Pathol. 2008;214:489–97.CrossRefPubMed
6.
7.
8.
Sun M, Liu X, Li JH, Yang JS, Zhang EB, Yin DD, et al. MiR-196a is up-regulated in gastric cancer and promotes cell proliferation by down-regulating p27kip1. Mol Cancer Ther. 2012;11:842–52.CrossRefPubMed
9.
Lu YC, Chen YJ, Wang HM, Tsai CY, Chen WH, Huang YC, et al. Oncogenic function and early detection potential of miRNA-10b in oral cancer as identified by microRNA profiling. Cancer Prev Res. 2012;5:665–74.CrossRef
10.
Li J, Huang H, Sun L, Yang M, Pan C, Chen W, et al. MiR-21 indicates poor prognosis in tongue squamous cell carcinomas as an apoptosis inhibitor. Clin Cancer Res. 2009;15:3998–4008.CrossRefPubMed
11.
Liu CJ, Lin SC, Yang CC, Cheng HW, Chang KW. Exploiting salivary miR-31 as a clinical biomarker of oral squamous cell carcinoma. Head Neck. 2012;34:219–24.CrossRefPubMed
12.
Hung PS, Chang KW, Kao SY, Chu TH, Liu CJ, Lin SC. Association between the rs2910164 polymorphism in pre-mir-146a and oral carcinoma progression. Oral Oncol. 2012;48:404–8.CrossRefPubMed
13.
Tanzer A, Amemiya CT, Kim CB, Stadler PF. Evolution of microRNAs located within Hox gene clusters. J Exp Zool B Mol Dev Evol. 2005;304:75–85.CrossRefPubMed
14.
Chen C, Zhang Y, Zhang L, Weakley SM, Yao Q. MicroRNA-196: critical roles and clinical applications in development and cancer. J Cell Mol Med. 2011;15:14–23.CrossRefPubMed
15.
Hornstein E, Mansfield JH, Yekta S, Hu JK, Harfe BD, McManus MT, et al. The microRNA miR-196 acts upstream of Hoxb8 and Shh in limb development. Nature. 2005;438:671–4.CrossRefPubMed
16.
Braig S, Mueller DW, Rothhammer T, Bosserhoff AK. MicroRNA miR-196a is a central regulator of HOX-B7 and BMP4 expression in malignant melanoma. Cell Mol Life Sci. 2010;67:3535–48.CrossRefPubMed
17.
Kawasaki H, Taira K. MicroRNA-196 inhibits HOXB8 expression in myeloid differentiation of HL60 cells. Nucleic Acids Symp Ser (Oxf). 2004;48:211–2.CrossRefPubMed
18.
Luthra R, Singh RR, Luthra MG, Li YX, Hannah C, Romans AM, et al. MicroRNA-196a targets annexin A1: a microRNA-mediated mechanism of annexin A1 downregulation in cancers. Oncogene. 2008;27:6667–78.CrossRefPubMed
19.
Bloomston M, Frankel WL, Petrocca F, Volinia S, Alder H, Hagan JP, et al. MicroRNA expression patterns to differentiate pancreatic adenocarcinoma from normal pancreas and chronic pancreatitis. JAMA. 2007;297:1901–8.CrossRefPubMed
20.
Guan Y, Mizoguchi M, Yoshimoto K, Hata N, Shono T, Suzuki SO, et al. MiRNA-196 is upregulated in glioblastoma but not in anaplastic astrocytoma and has prognostic significance. Clin Cancer Res. 2010;16:4289–97.CrossRefPubMed
21.
Li Y, Zhang M, Chen H, Dong Z, Ganapathy V, Thangaraju M, et al. Ratio of miR-196s to HOXC8 messenger RNA correlates with breast cancer cell migration and metastasis. Cancer Res. 2010;70:7894–904.CrossRefPubMed
22.
Schimanski CC, Frerichs K, Rahman F, Berger M, Lang H, Galle PR, et al. High miR-196a levels promote the oncogenic phenotype of colorectal cancer cells. World J Gastroenterol. 2009;15:2089–96.CrossRefPubMed
23.
Wang J, Chen J, Chang P, LeBlanc A, Li D, Abbruzzesse JL, et al. MicroRNAs in plasma of pancreatic ductal adenocarcinoma patients as novel blood-based biomarkers of disease. Cancer Prev Res. 2009;2:807–13.CrossRef
24.
Maru DM, Singh RR, Hannah C, Albarracin CT, Li YX, Abraham R, et al. MicroRNA-196a is a potential marker of progression during Barrett’s metaplasia–dysplasia–invasive adenocarcinoma sequence in esophagus. Am J Pathol. 2009;174:1940–8.CrossRefPubMed
25.
Christensen BC, Avissar-Whiting M, Ouellet LG, Butler RA, Nelson HH, McClean MD, et al. Mature microRNA sequence polymorphism in MIR196A2 is associated with risk and prognosis of head and neck cancer. Clin Cancer Res. 2010;16:3713–20.CrossRefPubMed
26.
Hu Z, Chen J, Tian T, Zhou X, Gu H, Xu L, et al. Genetic variants of miRNA sequences and non–small cell lung cancer survival. J Clin Invest. 2008;118:2600–8.PubMed
27.
Jedlinski DJ, Gabrovska PN, Weinstein SR, Smith RA, Griffiths LR. Single nucleotide polymorphism in hsa-mir-196a-2 and breast cancer risk: a case–control study. Twin Res Hum Genet. 2011;14:417–21.CrossRefPubMed
28.
Peng S, Kuang Z, Sheng C, Zhang Y, Xu H, Cheng Q. Association of microRNA-196a-2 gene polymorphism with gastric cancer risk in a Chinese population. Dig Dis Sci. 2010;55:2288–93.CrossRefPubMed
29.
Tian T, Shu Y, Chen J, Hu Z, Xu L, Jin G, et al. A functional genetic variant in microRNA-196a2 is associated with increased susceptibility of lung cancer in Chinese. Cancer Epidemiol Biomarkers Prev. 2009;18:1183–7.CrossRefPubMed
30.
Zhan JF, Chen LH, Chen ZX, Yuan YW, Xie GZ, Sun AM, et al. A functional variant in microRNA-196a2 is associated with susceptibility of colorectal cancer in a Chinese population. Arch Med Res. 2011;42:144–8.CrossRefPubMed
31.
Zhang M, Jin M, Yu Y, Zhang S, Wu Y, Liu H, et al. Associations of miRNA polymorphisms and female physiological characteristics with breast cancer risk in Chinese population. Eur J Cancer Care (Engl). 2012;21:274–80.CrossRef
32.
Mueller DW, Bosserhoff AK. MicroRNA miR-196a controls melanoma-associated genes by regulating HOX-C8 expression. Int J Cancer. 2011;129:1064–74.CrossRefPubMed
33.
Huang Q, Yu GP, McCormick SA, Mo J, Datta B, Mahimkar M, et al. Genetic differences detected by comparative genomic hybridization in head and neck squamous cell carcinomas from different tumor sites: construction of oncogenetic trees for tumor progression. Genes Chromosomes Cancer. 2002;34:224–33.CrossRefPubMed
34.
Liu CJ, Kao SY, Tu HF, Tsai MM, Chang KW, Lin SC. Increase of microRNA miR-31 level in plasma could be a potential marker of oral cancer. Oral Dis. 2010;16:360–4.CrossRefPubMed
35.
Kong X, Du Y, Wang G, Gao J, Gong Y, Li L, et al. Detection of differentially expressed microRNAs in serum of pancreatic ductal adenocarcinoma patients: miR-196a could be a potential marker for poor prognosis. Dig Dis Sci. 2011;56:602–9.CrossRefPubMed
36.
Hoffman AE, Zheng T, Yi C, Leaderer D, Weidhaas J, Slack F, et al. microRNA miR-196a-2 and breast cancer: a genetic and epigenetic association study and functional analysis. Cancer Res. 2009;69:5970–7.CrossRefPubMed
Metadata
Title
miR-196a Overexpression and miR-196a2 Gene Polymorphism Are Prognostic Predictors of Oral Carcinomas
Authors
Chung-Ji Liu, DDS, MS
Meng-Miao Tsai, PhD
Hsi-Feng Tu, DDS, PhD
Man-Tin Lui, DDS
Hui-Wen Cheng, MS
Shu-Chun Lin, PhD
Publication date
01-12-2013
Publisher
Springer US
Published in
Annals of Surgical Oncology / Issue Special Issue 3/2013
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-012-2618-6

Other articles of this Special Issue 3/2013

Annals of Surgical Oncology 3/2013 Go to the issue

Translational Research and Biomarkers

Expression of GOLM1 Correlates with Prognosis in Human Hepatocellular Carcinoma

Translational Research and Biomarkers

Expression of Brachyury Gene Is a Significant Prognostic Factor for Primary Lung Carcinoma

Translational Research and Biomarkers

A Large Cohort of Consecutive Patients Confirmed Frequent HER2 Positivity in Gastric Carcinomas with Advanced Stages

Translational Research and Biomarkers

The Cost-Effectiveness of Neoadjuvant Chemoradiation is Superior to a Surgery-First Approach in the Treatment of Pancreatic Head Adenocarcinoma

Translational Research and Biomarkers

Pancreatic Ductal Adenocarcinoma is Associated with a Distinct Urinary Metabolomic Signature

Translational Research and Biomarkers

Increased BCAR1 Predicts Poor Outcomes of Non-small Cell Lung Cancer in Multiple-Center Patients