MicroRNA-211 Enhances The Oncogenicity Of Carcinogen-Induced Oral Carcinoma By Repressing TCF12 And Increasing Antioxidant Activity.
Yi-Fen Chen, Cheng-Chieh Yang, Shou-Yen Kao, Chung-Ji Liu, Shu-Chun Lin, Kuo-Wei Chang
Published 2016 · Medicine, Biology
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miR-211 expression in human oral squamous cell carcinoma (OSCC) has been implicated in poor patient survival. To investigate the oncogenic roles of miR-211, we generated K14-EGFP-miR-211 transgenic mice tagged with GFP. Induction of oral carcinogenesis in transgenic mice using 4-nitroquinoline 1-oxide (4NQO) resulted in more extensive and severe tongue tumorigenesis compared with control animals. We found that 4NQO and arecoline upregulated miR-211 expression in OSCC cells. In silico and experimental evidence further revealed that miR-211 directly targeted transcription factor 12 (TCF12), which mediated suppressor activities in OSCC cells and was drastically downregulated in tumor tissues. We used GeneChip analysis and bioinformatic algorithms to identify transcriptional targets of TCF12 and confirmed through reporter and ChIP assays that family with sequence similarity 213, member A (FAM213A), a peroxiredoxin-like antioxidative protein, was repressed transcriptionally by TCF12. FAM213A silencing in OSCC cells diminished oncogenic activity, reduced the ALDH1-positive cell population, and increased reactive oxygen species. TCF12 and FAM213A expression was correlated inversely in head and neck carcinoma samples according to The Cancer Genome Atlas. OSCC patients bearing tumors with high FAM213A expression tended to have worse survival. Furthermore, 4NQO treatment downregulated TCF12 and upregulated FAM213A by modulating miR-211 both in vitro and in vivo Overall, our findings develop a mouse model that recapitulates the molecular and histopathologic alterations of human OSCC pathogenesis and highlight a new miRNA-mediated oncogenic mechanism. Cancer Res; 76(16); 4872-86. ©2016 AACR.
This paper references
Clinical evidence of field cancerization in patients with oral cavity cancer in a betel on May 27, 2016
CT Liao (2016)
Peroxiredoxin Functions as a Peroxidase and a Regulator and Sensor of Local Peroxides*
Sue Goo Rhee (2011)
Epigenetic Regulation of miRNA-211 by MMP-9 Governs Glioma Cell Apoptosis, Chemosensitivity and Radiosensitivity
Swapna Asuthkar (2012)
MicroRNAs in Stress Signaling and Human Disease
Joshua T Mendell (2012)
K14-EGFP-miR-31 transgenic mice have high susceptibility to on May 27, 2016
SH Tseng (2016)
Genome-wide analysis of putative peroxiredoxin in unicellular and filamentous cyanobacteria
Hongli Cui (2012)
IGF-1R, a target of let-7b, mediates crosstalk between IRS-2/Akt and MAPK pathways to promote proliferation of oral squamous cell carcinoma
L. Gao (2014)
miR-211 promotes the progression of head and neck carcinomas by targeting TGFβRII.
Ting-Hui Chu (2013)
New Target Genes of MITF-Induced microRNA-211 Contribute to Melanoma Cell Invasion
Christiane Margue (2013)
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)
The clinical impact of HPV tumor status upon head and neck squamous cell carcinomas.
Eleni M Benson (2014)
Stem Cell Marker (Nanog) and Stat-3 Signaling Promote MicroRNA-21 Expression and Chemoresistance in Hyaluronan/CD44-activated Head and Neck Squamous Cell Carcinoma Cells
Lilly Y. w. Bourguignon (2012)
Gene expression profiling in human fetal liver and identification of tissue- and developmental-stage-specific genes through compiled expression profiles and efficient cloning of full-length cDNAs.
Y. Yu (2001)
PAMM: a redox regulatory protein that modulates osteoclast differentiation.
Y. Xu (2010)
The molecular biology of head and neck cancer
C. René Leemans (2011)
Microphthalmia-associated Transcription Factor (MITF) Promotes Differentiation of Human Retinal Pigment Epithelium (RPE) by Regulating microRNAs-204/211 Expression*
Jeffrey Adijanto (2012)
miR-31 is upregulated in oral premalignant epithelium and contributes to the immortalization of normal oral keratinocytes.
Pei-Shih Hung (2014)
MicroRNA-211 Expression Promotes Colorectal Cancer Cell Growth In Vitro and In Vivo by Targeting Tumor Suppressor CHD5
Chunxiao Cai (2012)
MicroRNA aberrances in head and neck cancer: pathogenetic and clinical significance
Hsi-Feng Tu (2013)
HEB, a helix-loop-helix protein related to E2A and ITF2 that can modulate the DNA-binding ability of myogenic regulatory factors.
J. Hu (1992)
EGF Up-Regulates miR-31 through the C/EBPβ Signal Cascade in Oral Carcinoma
Wen-cheng Lu (2014)
Gene expression profiling in human fetal liver and identification of tissue- and developmental-stage-specific genes through compiled expression profiles and on May 27, 2016
Y Yu (2016)
Embryonic myogenesis pathways in muscle regeneration.
P. Zhao (2004)
E protein function in lymphocyte development.
M. W. Quong (2002)
JASPAR 2014: an extensively expanded and updated open-access database of transcription factor binding profiles
Anthony Mathelier (2014)
Association between High miR-211 microRNA Expression and the Poor Prognosis of Oral Carcinoma
K-W Chang (2008)
Targeting antioxidants for cancer therapy.
Andrea Glasauer (2014)
ATDC induces an invasive switch in KRAS-induced pancreatic tumorigenesis.
Lidong Wang (2015)
ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome.
C. Ginestier (2007)
Tumor suppressive microRNA-218 inhibits cancer cell migration and invasion through targeting laminin-332 in head and neck squamous cell carcinoma
Takashi Kinoshita (2012)
miR-211 is a prosurvival microRNA that regulates chop expression in a PERK-dependent manner.
Nilesh Chitnis (2012)
Molecular and cellular cues of diet-associated oral carcinogenesis--with an emphasis on areca-nut-induced oral cancer development.
Wan-Chun Li (2015)
The Regulation of miRNA-211 Expression and Its Role in Melanoma Cell Invasiveness
Joseph Mazar (2010)
Differential expression of microRNAs in 2-cell and 4-cell mouse embryos.
Pei Wang (2014)
TRIM29 suppresses TWIST1 and invasive breast cancer behavior.
L. Ai (2014)
miR-134 induces oncogenicity and metastasis in head and neck carcinoma through targeting WWOX gene.
Chung-Ji Liu (2014)
The increase of oncogenic miRNA expression in tongue carcinogenesis of a mouse model.
Yu-Yu Kao (2015)
Oxidative stress inhibits distant metastasis by human melanoma cells
Elena Piskounova (2015)
Expression of the bHLH transcription factor Tcf12 (ME1) gene is linked to the expansion of precursor cell populations during neurogenesis.
Martine Uittenbogaard (2002)
LncRNA loc285194 is a p53-regulated tumor suppressor
Qian Liu (2013)
A Novel Candidate Region for Genetic Adaptation to High Altitude in Andean Populations
Guido Valverde (2015)
The bHLH transcription factor Tcf12 (ME1) mRNA is abundantly expressed in Paneth cells of mouse intestine.
Y. Tanigawa (2007)
MiR-204 promotes apoptosis in oxidative stress-induced rat Schwann cells by suppressing neuritin expression.
Rui Gao (2014)
microRNAs expression predicts local recurrence risk in oral squamous cell carcinoma
F Ganci (2014)
Clinical evidence of field cancerization in patients with oral cavity cancer in a betel quid chewing area.
Chun-ta Liao (2014)
Mutations in TCF12, encoding a basic helix-loop-helix partner of TWIST1, are a frequent cause of coronal craniosynostosis
Vikram Sharma (2013)
TCF12 Protein Functions as Transcriptional Repressor of E-cadherin, and Its Overexpression Is Correlated with Metastasis of Colorectal Cancer*
Chun-Chung Hsin-Yi Lee (2011)
Distinct subpopulations of head and neck cancer cells with different levels of intracellular reactive oxygen species exhibit diverse stemness, proliferation, and chemosensitivity.
Ching-Wen Chang (2014)
Nrf2 enhances resistance of cancer cells to chemotherapeutic drugs, the dark side of Nrf2.
X. Wang (2008)
Extraskeletal myxoid chondrosarcoma with a t(9;16)(q22;p11.2) resulting in a NR4A3-FUS fusion.
Cory Broehm (2014)
miR-31 ablates expression of the HIF regulatory factor FIH to activate the HIF pathway in head and neck carcinoma.
Chung-Ji Liu (2010)
Potent intracellular oxidative stress exerted by the carcinogen 4-nitroquinoline-N-oxide.
T. Nunoshiba (1993)
Helix-Loop-Helix Proteins: Regulators of Transcription in Eucaryotic Organisms
M. Massari (2000)
This paper is referenced by
Downregulation of miR-377 Promotes Oral Squamous Cell Carcinoma Growth and Migration by Targeting HDAC9
Bhawna Rastogi (2017)
Long non‐coding RNA F11‐AS1 inhibits HBV‐related hepatocellular carcinoma progression by regulating NR1I3 via binding to microRNA‐211‐5p
Yibin Deng (2019)
MiR-129-5p Inhibits Proliferation and Invasion of Chondrosarcoma Cells by Regulating SOX4/Wnt/β-Catenin Signaling Pathway
Peng Zhang (2017)
FAT1 somatic mutations in head and neck carcinoma are associated with tumor progression and survival
Shu-Chun Lin (2018)
Establishing of mouse oral carcinoma cell lines derived from transgenic mice and their use as syngeneic tumorigenesis models
Yi-Fen Chen (2019)
Quantification of structural and microvascular changes for diagnosing early-stage oral cancer.
Ping-Hsien Chen (2020)
DEAD-Box Helicase 5 Interacts With Transcription Factor 12 and Promotes the Progression of Osteosarcoma by Stimulating Cell Cycle Progression
Yanchun Chen (2019)
Influence of Tea Consumption on the Development of Second Esophageal Neoplasm in Patients with Head and Neck Cancer
Yao-Kuang Wang (2019)
Combination of structural and vascular optical coherence tomography for differentiating oral lesions of mice in different carcinogenesis stages.
Ping-Hisen Chen (2018)
MTA3-SOX2 Module Regulates Cancer Stemness and Contributes to Clinical Outcomes of Tongue Carcinoma
Zhimeng Yao (2019)
Novel circulating microRNAs expression profile in colon cancer: a pilot study
Ya-Nan Wang (2017)
MicroRNA miR-31 targets SIRT3 to disrupt mitochondrial activity and increase oxidative stress in oral carcinoma.
Yu-Yu Kao (2019)
Mouse Tumor-Bearing Models as Preclinical Study Platforms for Oral Squamous Cell Carcinoma
Qianwen Li (2020)
microRNA‐211 promotes proliferation, migration, and invasion ability of oral squamous cell carcinoma cells via targeting the bridging integrator 1 protein
Jiabao Zheng (2019)
Prospective applications of microRNAs in oral cancer
Chuan Fang (2019)
Integrated phenotypic screening and activity-based protein profiling to reveal potential therapy targets of pancreatic cancer.
Wenyan Liu (2019)
p‐Hydroxylcinnamaldehyde slows the progression of 4NQO‐induced oesophageal tumourigenesis via the RhoA‐MAPK signaling pathway
Lianmei Zhao (2018)
Targeting Cellular Metabolism Modulates Head and Neck Oncogenesis
Y P Hsieh (2019)
Search for useful biomarkers in hepatocellular carcinoma, tumor factors and background liver factors (Review).
Dai Shimizu (2017)
High expression of TCF12 contributes to gastric cancer development via being target regulated by miR-183 and activating PI3K/AKT pathway.
Xuekui Wang (2019)
mRNA and P-element-induced wimpy testis-interacting RNA profile in chemical-induced oral squamous cell carcinoma mice model
Lihong Wu (2019)
Preclinical models of head and neck squamous cell carcinoma for a basic understanding of cancer biology and its translation into efficient therapies
Ingeborg Tinhofer (2020)
MiR-223 promotes oral squamous cell carcinoma proliferation and migration by regulating FBXW7
Lihua Jiang (2019)
HSP40 co-chaperone protein Tid1 suppresses metastasis of head and neck cancer by inhibiting Galectin-7-TCF3-MMP9 axis signaling
Yu-Syuan Chen (2018)
miR-134 targets PDCD7 to reduce E-cadherin expression and enhance oral cancer progression.
Shih-Yuan Peng (2018)
TCF12 overexpression as a poor prognostic factor in ovarian cancer.
Sainan Gao (2019)
TCF 12 promotes the tumorigenesis and metastasis of hepatocellular carcinoma via upregulation of CXCR 4 expression
Jing Yang (2019)
Targeting of miR‐31/96/182 to the Numb gene during head and neck oncogenesis
Chung-Hsien Chou (2018)
Long non-coding RNA FTH1P3 facilitates oral squamous cell carcinoma progression by acting as a molecular sponge of miR-224-5p to modulate fizzled 5 expression.
C. Zhang (2017)
Long intergenic non-coding RNA 668 regulates VEGFA signaling through inhibition of miR-297 in oral squamous cell carcinoma.
C. Zhang (2017)
The miR-372-ZBTB7A Oncogenic Axis Suppresses TRAIL-R2 Associated Drug Sensitivity in Oral Carcinoma
Li-Yin Yeh (2020)
University of Groningen MTA3-SOX2 Module Regulates Cancer Sternness and Contributes to Clinical Outcomes of Tongue Carcinoma Yao,
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