The Increase Of Oncogenic MiRNA Expression In Tongue Carcinogenesis Of A Mouse Model.
Yu-Yu Kao, Hsi-Feng Tu, Shou-Yen Kao, Kuo-Wei Chang, Shu-Chun Lin
Published 2015 · Medicine, Biology
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OBJECTIVES This study investigated the oncogenic miRNA level in the tissue and biofluids in the Nitroquinoline 1-Oxide (4NQO)-induced mouse tongue carcinogenesis model for potential diagnostic or therapeutic application. MATERIALS AND METHODS The histological examination, immunohistochemistry, in situ hybridization, quantitative PCR analysis and bioinformatic algorithms were performed to unravel the signaling activation and miRNA expression in female murine samples. RESULTS The increase of miR-21 and miR-31 staining, and EGFR activation paralleled the severity of 4NQO-induced epithelial pathogenesis in tongue epithelium. A progressive increase of miR-21, miR-31 and miR-146a in both saliva and plasma samples was also noted. miR-31 was the earliest emerging miRNA in the saliva. The increase of plasma miR-146a, miR-184 and miR-372 was detectable early in the induction, and it was particularly eminent at the most advanced lesion state. The combined analysis of the multiple oncogenic miRNAs in the plasma signified a potent discriminative capacity between normal and pathological states. As the blockage of EGFR or AKT activation drastically reverted the miR-21, miR-31 and miR-146a expression induced by 4NQO in human oral carcinoma cell lines, the results implicated a mechanistic linkage of the oncogenic miRNAs' induction through EGFR/AKT activation. CONCLUSIONS In this study, we show the dysregulation of oncogenic miRNAs in murine tongue tumorigenesis, which simulates human counterparts. Increased multiple miRNAs in the biofluids may be valuable non-invasive markers in detecting oral carcinogenesis at an early stage. This animal model may also be useful for developing liquid biopsies and prevention strategies against oral carcinoma by abrogating EGFR or oncogenic miRNAs.
This paper references
MiR-21 Expression in the Tumor Stroma of Oral Squamous Cell Carcinoma: An Independent Biomarker of Disease Free Survival
Nora Hedbäck (2014)
Dysregulation of miR-31 and miR-21 induced by zinc deficiency promotes esophageal cancer.
Hansjürg Alder (2012)
K14-EGFP-miR-31 transgenic mice have high susceptibility to chemical-induced squamous cell tumorigenesis that is associating with Ku80 repression.
Ssu-Hsueh Tseng (2015)
MicroRNA let-7a represses chemoresistance and tumourigenicity in head and neck cancer via stem-like properties ablation.
Cheng-Chia Yu (2011)
Alterations of Rb Pathway Components Are Frequent Events in Patients with Oral Epithelial Dysplasia and Predict Clinical Outcome in Patients with Squamous Cell Carcinoma
Shilpi Soni (2005)
Mature miR-184 as Potential Oncogenic microRNA of Squamous Cell Carcinoma of Tongue
Thian-Sze Wong (2008)
Association between the rs2910164 polymorphism in pre-mir-146a and oral carcinoma progression.
Pei-Shi Hung (2012)
The role of the TP53 gene during rat tongue carcinogenesis induced by 4-nitroquinoline 1-oxide.
Eliana Maria Minicucci (2011)
MicroRNA-138 suppresses epithelial-mesenchymal transition in squamous cell carcinoma cell lines.
Xiqiang Liu (2011)
Genomewide Study of Salivary MicroRNAs for Detection of Oral Cancer
Fatemeh Momen-Heravi (2014)
S100A7 overexpression is a predictive marker for high risk of malignant transformation in oral dysplasia.
Jatinder Kaur (2014)
Serum CCL2 and CCL3 as potential biomarkers for the diagnosis of oral squamous cell carcinoma
Liang Ding (2014)
The molecular biology of head and neck cancer
C. René Leemans (2011)
miR-211 promotes the progression of head and neck carcinomas by targeting TGFβRII.
Ting-Hui Chu (2013)
MicroRNA aberrances in head and neck cancer: pathogenetic and clinical significance
Hsi-Feng Tu (2013)
Risk Stratification in Oral Cavity Squamous Cell Carcinoma by Preoperative CRP and SCC Antigen Levels
Shiang-Fu Huang (2012)
Predictive Role of p53 Protein as a Single Marker or Associated with ki67 Antigen in Oral Leukoplakia: A Retrospective Longitudinal Study
Davide Bartolomeo Gissi (2015)
Chemopreventive effect of a mixture of Chinese Herbs (antitumor B) on chemically induced oral carcinogenesis.
Yian Wang (2013)
Circulating miRNA is a novel marker for head and neck squamous cell carcinoma
Cheng-Ming Hsu (2012)
Lin28B/Let-7 Regulates Expression of Oct4 and Sox2 and Reprograms Oral Squamous Cell Carcinoma Cells to a Stem-like State.
Chian-Shiu Chien (2015)
Tetraspanins CD9 and CD151, epidermal growth factor receptor and cyclooxygenase-2 expression predict malignant progression in oral epithelial dysplasia
Paul Nankivell (2013)
Prevalidation of Salivary Biomarkers for Oral Cancer Detection
David Elashoff (2012)
miR-372 inhibits p62 in head and neck squamous cell carcinoma in vitro and in vivo
Li-Yin Yeh (2015)
miR-24 up-regulation in oral carcinoma: positive association from clinical and in vitro analysis.
Shu-Chun Lin (2010)
Association of aberrant p53 and p21(WAF1) immunoreactivity with the outcome of oral verrucous leukoplakia in Taiwan.
Kuo-Wei Chang (2000)
Exploiting salivary miR-31 as a clinical biomarker of oral squamous cell carcinoma.
Chung-Ji Liu (2012)
miR-31 is upregulated in oral premalignant epithelium and contributes to the immortalization of normal oral keratinocytes.
Pei-Shih Hung (2014)
miR-146a Enhances the Oncogenicity of Oral Carcinoma by Concomitant Targeting of the IRAK1, TRAF6 and NUMB Genes
Pei-Shi Hung (2013)
The relevance of EGFR overexpression for the prediction of the malignant transformation of oral leukoplakia.
J. Ries (2013)
Salivary Transcriptome Diagnostics for Oral Cancer Detection
Yang Li (2004)
Gain of hTERC: a genetic marker of malignancy in oral potentially malignant lesions.
Tshering Dorji (2015)
Frequent microsatellite alterations at chromosomes 9p21 and 3p14 in oral premalignant lesions and their value in cancer risk assessment
L. Mao (1996)
miR-31 ablates expression of the HIF regulatory factor FIH to activate the HIF pathway in head and neck carcinoma.
Chung-Ji Liu (2010)
Increase of microRNA miR-31 level in plasma could be a potential marker of oral cancer.
C-J Liu (2010)
Overexpression of caldesmon is associated with lymph node metastasis and poorer prognosis in patients with oral cavity squamous cell carcinoma.
K P Chang (2013)
Loss of miR-125b-1 contributes to head and neck cancer development by dysregulating TACSTD2 and MAPK pathway
Hajimu Nakanishi (2014)
Programmed cell death 4 loss increases tumor cell invasion and is regulated by miR-21 in oral squamous cell carcinoma
P. Pintor dos Reis (2010)
Podoplanin: a novel marker for oral cancer risk in patients with oral premalignancy.
H. Kawaguchi (2008)
Protective effect of Spirulina against 4-nitroquinoline-1-oxide induced toxicity
Vijaya Padma Viswanadha (2010)
MicroRNA-200c attenuates tumour growth and metastasis of presumptive head and neck squamous cell carcinoma stem cells.
Wen-liang Lo (2011)
EGF Up-Regulates miR-31 through the C/EBPβ Signal Cascade in Oral Carcinoma
Wen-cheng Lu (2014)
Salivary microRNA: Discovery, Characterization, and Clinical Utility for Oral Cancer Detection
Noh Jin Park (2009)
Molecular screening of oral precancer.
A. Peggy Graveland (2013)
Circulating microRNA-21 (MIR-21) and phosphatase and tensin homolog (PTEN) are promising novel biomarkers for detection of oral squamous cell carcinoma
Wenhao Ren (2014)
MiR-21 Indicates Poor Prognosis in Tongue Squamous Cell Carcinomas as an Apoptosis Inhibitor
Jinsong Li (2009)
Suprabasal p53 immunoexpression is strongly associated with high grade dysplasia and risk for malignant transformation in potentially malignant oral lesions from Northern Ireland.
I. Cruz (2002)
Analysis of plasma metabolic biomarkers in the development of 4-nitroquinoline-1-oxide-induced oral carcinogenesis in rats
Xiangli Kong (2015)
Discovery and Prevalidation of Salivary Extracellular microRNA Biomarkers Panel for the Noninvasive Detection of Benign and Malignant Parotid Gland Tumors
Johannes H. Matse (2013)
NF-κB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses
K. Taganov (2006)
Allelic imbalance at chromosomal loci implicated in the pathogenesis of oral precancer, cumulative loss and its relationship with progression to cancer.
Max Partridge (1998)
Epidermal Growth Factor Receptor Expression and Gene Copy Number in the Risk of Oral Cancer
Mohammed Taoudi Benchekroun (2010)
miR-181 as a putative biomarker for lymph-node metastasis of oral squamous cell carcinoma.
Cheng-Chieh Yang (2011)
miR-27b-regulated TCTP as a novel plasma biomarker for oral cancer: from quantitative proteomics to post-transcriptional study.
Wan-Yu Lo (2012)
This paper is referenced by
Specific deletion of p16INK4a with retention of p19ARF enhances the development of invasive oral squamous cell carcinoma.
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Tami Yap (2018)
miR-31-5p Is a Potential Circulating Biomarker and Therapeutic Target for Oral Cancer
Zhiyuan Lu (2019)
Head and Neck Cancer: Epidemiology and Role of MicroRNAs
Muhammad Babar Khawar (2017)
MicroRNA-31 upregulation predicts increased risk of progression of oral potentially malignant disorder.
Kai-Feng Hung (2016)
Oral Oncogenesis and Chemoprevention
Toshitaka Tanaka (2017)
Establishment of syngeneic murine model for oral cancer therapy.
Yi-Fen Chen (2019)
MicroRNAs in human tongue squamous cell carcinoma: From pathogenesis to therapeutic implications.
Omer Faruk Karatas (2017)
MicroRNA-211 Enhances the Oncogenicity of Carcinogen-Induced Oral Carcinoma by Repressing TCF12 and Increasing Antioxidant Activity.
Yi-Fen Chen (2016)
Loss of Function of Canonical Notch Signaling Drives Head and Neck Carcinogenesis
Patrick E Nyman (2018)
Prospective applications of microRNAs in oral cancer
Chuan Fang (2019)
Mouse Tumor-Bearing Models as Preclinical Study Platforms for Oral Squamous Cell Carcinoma
Qianwen Li (2020)
miR-93-5p may be an important oncogene in prostate cancer by bioinformatics analysis.
Yuemei Yang (2019)
Targeting Cellular Metabolism Modulates Head and Neck Oncogenesis
Y P Hsieh (2019)
miR-134 targets PDCD7 to reduce E-cadherin expression and enhance oral cancer progression.
Shih-Yuan Peng (2018)
Genetics and Molecular Mechanisms in Oral Cancer Progression
Prashanth Panta (2019)
Establishing of mouse oral carcinoma cell lines derived from transgenic mice and their use as syngeneic tumorigenesis models
Yi-Fen Chen (2019)
Role of salivary transcriptomics as potential biomarkers in oral cancer: A systematic review.
S. Patil (2019)