• DNA methylation
• RNA expression
• Salivary biomarkers
• epigenetic modifications.
• oral cancer
• tumor suppressor genes

• Humans
• Mouth Neoplasms/diagnosis
• Mouth Neoplasms/genetics
• Saliva/chemistry
• Saliva/metabolism
• Biomarkers, Tumor/genetics
• Biomarkers, Tumor/analysis
• Early Detection of Cancer/methods

Recent studies have shown aberrant expression of micro-RNAs in cancer-associated fibroblasts (CAFs). This study aimed to investigate miR-138 dysregulation in CAFs in oral squamous cell carcinoma (OSCC) and its effects on their phenotype and invasion of adjacent OSCC cells.

Expression of miR-138 was first investigated in OSCC lesions (n = 53) and OSCC-derived CAFs (n = 15). MiR-138 mimics and inhibitors were used to functionally investigate the role of miR-138 on CAF phenotype and the resulting change in their ability to support OSCC invasion.

Expression of miR-138 showed marked heterogeneity in both OSCC tissues and cultured fibroblasts. Ectopic miR-138 expression reduced fibroblasts’ motility and collagen contraction ability and suppressed invasion of suprajacent OSCC cells, while its inhibition resulted in the opposite outcome. Transcript and protein examination after modulation of miR-138 expression showed changes in CAF phenotype-specific molecules, focal adhesion kinase axis, and TGFβ1 signaling pathway.

Despite its heterogeneous expression, miR-138 in OSCC-derived CAFs exhibits a tumor-suppressive function.

• Norges Forskningsråd
• Helse Vest
• Senter for Internasjonalisering av Utdanning

Background: Knowledge on the role of miR changes in tumor stroma for cancer progression is limited. This study aimed to investigate the role of miR dysregulation in cancer-associated fibroblasts (CAFs) in oral squamous cell carcinoma (OSCC). Methodology: CAF and normal oral fibroblasts (NOFs) were isolated from biopsies of OSCC patients and healthy individuals after informed consent and grown in 3D collagen gels. Total RNA was extracted. Global miR expression was profiled using Illumina version 2 panels. The functional impact of altered miR-204 expression in fibroblasts on their phenotype and molecular profile was investigated using mimics and inhibitors of miR-204. Further, the impact of miR-204 expression in fibroblasts on invasion of adjacent OSCC cells was assessed in 3D-organotypic co-cultures. Results: Unsupervised hierarchical clustering for global miR expression resulted in separate clusters for CAF and NOF. SAM analysis identified differential expression of twelve miRs between CAF and NOF. Modulation of miR-204 expression did not affect fibroblast cell proliferation, but resulted in changes in the motility phenotype, expression of various motility-related molecules, and invasion of the adjacent OSCC cells. 3′ UTR miR target reporter assay showed ITGA11 to be a direct target of miR-204. Conclusions: This study identifies differentially expressed miRs in stromal fibroblasts of OSCC lesions compared with normal oral mucosa and it reveals that one of the significantly downregulated miRs in CAF, miR-204, has a tumor-suppressive function through inhibition of fibroblast migration by modulating the expression of several different molecules in addition to directly targeting ITGA11.

• ITGA11
• fibroblasts
• miR-204
• oral squamous cell carcinoma
• tumor stroma

• P30 CA086862 NCI NIH HHS
• L30 DE029070 NIDCR NIH HHS
• P01 CA098101 NCI NIH HHS
• P30 CA013696 NCI NIH HHS
• R50 CA243692 NCI NIH HHS
• R01 AA026297 NIAAA NIH HHS
• P30 ES009089 NIEHS NIH HHS

MicroRNAs (miRNAs) are widely believed to be promising targets for oral squamous cell carcinoma (OSCC) gene therapy. miR-214 has been identified as a promoter of OSCC aggression and metastasis.

Graphene oxide-polyethylenimine (GO-PEI) complexes were prepared and loaded with a miRNA inhibitor at different N/P ratios. The transfection efficiency of GO-PEI-inhibitor was tested in Cal27 and SCC9 cells. Moreover, the tumor inhibition ability of GO-PEI-inhibitor was measured in an OSCC xenograft mouse model by intratumoral injection.

Here, we show that a GO-PEI complex efficiently delivers a miR-214 inhibitor into OSCC cells and controls the intracellular release of the miR-214 inhibitor. These results indicate that the GO-PEI-miR-214 inhibitor complex efficiently inhibited cellular miR-214, resulting in a decrease in OSCC cell invasion and migration and an increase in cell apoptosis by targeting PTEN and p53. In the xenograft mouse model, the GO-PEI-miR-214 inhibitor complex significantly prevented tumor volume growth.

This study indicates that functionalized GO-PEI with low toxicity has promising potential for miRNA delivery for the treatment of OSCC.

• GO-PEI
• gene therapy
• miR-214 inhibitor
• oral squamous cell carcinoma

For early‐stage oral squamous cell carcinoma (OSCC), there is no existing risk‐stratification modality beyond conventional TNM staging system to identify patients at high risk for cancer‐specific mortality.

A total of 568 early‐stage OSCC patients who had surgery only and also with available 5‐year clinical outcomes data were identified. Signature microRNAs (miRNAs) were discovered using deep sequencing analysis and validated by qRT‐PCR. The final 5‐plex prognostic marker panel was utilized to generate a cancer‐specific mortality risk score using the multivariate Cox regression analyses. The prognostic markers were validated in the internal and external validation cohorts.

The risk score from the 5‐plex marker panel consisting of miRNAs‐127‐3p, 4736, 655‐3p, TNM stage and histologic grading stratified patients into four risk categories. Compared to the low‐risk group, the high‐risk group had 23‐fold increased mortality risk (hazard ratio 23, 95% confidence interval 13‐42), with a median time‐to‐recurrence of 6 months and time‐to‐death of 11 months (vs >60 months for each among low‐risk patient; p < .001).

The miRNA‐based 5‐plex marker panel driven mortality risk score formula provides clinically practical and reliable measures to assess the prognosis of patients assigned to an early‐stage OSCC.

• deep sequencing
• microRNA
• oral squamous cell carcinoma
• prognostic marker
• risk score

• head and neck squamous cell carcinomas
• human papilloma virus
• miRNAs
• saliva

For patients with head and neck squamous cell carcinoma (HNSCC), survival rates have not improved due to local recurrence and distant metastasis. Current targeted molecular therapies do not substantially benefit HNSCC patients. Therefore, it is necessary to use advanced genomic approaches to elucidate the molecular mechanisms underlying the aggressiveness of HNSCC cells. Analysis of our microRNA (miRNA) expression signature by RNA sequencing showed that the miR‐199 family (miR‐199a‐5p, miR‐199a‐3p, miR‐199b‐5p and miR‐199b‐3p) was significantly reduced in cancer tissues. Ectopic expression of mature miRNA demonstrated that all members of the miR‐199 family inhibited cancer cell migration and invasion by HNSCC cell lines (SAS and HSC3). These findings suggested that both passenger strands and guide strands of miRNA are involved in cancer pathogenesis. In silico database and genome‐wide gene expression analyses revealed that the gene coding for integrin α3 (ITGA3) was regulated by all members of the miR‐199 family in HNSCC cells. Knockdown of ITGA3 significantly inhibited cancer cell migration and invasion by HNSCC cells. Moreover, overexpression of ITGA3 was confirmed in HNSCC specimens, and high expression of ITGA3 predicted poorer survival of the patients (P = 0.0048). Our data revealed that both strands of pre‐miR‐199a (miR‐199a‐5p and miR‐199a‐3p) and pre‐miR‐199b (miR‐199b‐5p and miR‐199b‐3p) acted as anti‐tumor miRNA in HNSCC cells. Importantly, the involvement of passenger strand miRNA in the regulation of cellular processes is a novel concept in RNA research. Novel miRNA‐based approaches for HNSCC can be used to identify potential targets for the development of new therapeutic strategies.

• ITGA3
• miR-199a
• miR-199b
• Anti-tumor
• head and neck squamous cell carcinoma

• microRNA
• oral cavity cancer
• squamous cell carcinoma
• young patients

• Biomarkers
• Early detection
• Head and neck squamous cell carcinoma
• Molecular level
• Prognosis

Oral cancer, represented mainly by oral squamous cell carcinoma (OSCC), is the eighth most common type of human cancer worldwide. The number of new OSCC cases is increasing worldwide, especially in the low-income countries, and the prognosis remains poor in spite of recent advances in the diagnostic and therapeutic modalities. MicroRNAs (miRNAs), 18–25 nucleotides long noncoding RNA molecules, have recently gained significant attention as potential regulators and biomarkers for carcinogenesis. Recent data show that several miRNAs are deregulated in OSCC, and they have either a tumor suppressive or an oncogenic role in oral carcinogenesis. This review summarizes current knowledge on the role of miRNAs as tumor promotors or tumor suppressors in OSCC development and discusses their potential value as diagnostic and prognostic markers in OSCC.

Incidence of head and neck squamous cell carcinoma (HNSCC) has continuously increased in past years while its survival rate has not been significantly improved. There is a critical need to better understand the genetic regulation of HNSCC tumorigenesis and progression. In this study, we comprehensively analyzed the function of miRNA-128 (miR-128) in the regulation of HNSCC growth and its putative targets in vitro and in vivo systems.

The function and targets of miR-128 were investigated in human HNSCC cell lines (JHU-13 and JHU-22), which were stably transfected with the miR-128 gene using a lentiviral delivery system. The expression levels of miR-128 and its targeted proteins were analyzed with qRT-PCR, Western blotting and flow cytometry. The binding capacity of miRNA-128 to its putative targets was determined using a luciferase report assay. MTT, colony formation, and a tumor xenograft model further evaluated the effects of miR-128 on HNSCC growth.

We generated two miR-128 stably transfected human HNSCC cell lines (JHU-13^miR-128 and JHU-22^miR-128). Enforced expression of miR-128 was detected in both cultured JHU-13^miR-128 and JHU-22^miR-128 cell lines, approximately seventeen to twenty folds higher than in vector control cell lines. miRNA-128 was able to bind with the 3′-untranslated regions of BMI-1, BAG-2, BAX, H3f3b, and Paip2 mRNAs, resulting in significant reduction of the targeted protein levels. We found that upregulated miR-128 expression significantly inhibited both JHU-13^miR-128 and JHU-22^miR-128 cell viability approximately 20 to 40%, and the JHU-22^miR-128 tumor xenograft growth compared to the vector control groups.

miR-128 acted as a tumor suppressor inhibiting the HNSCC growth by directly mediating the expression of putative targets. Our results provide a better understanding of miRNA-128 function and its potential targets, which may be valuable for developing novel diagnostic markers and targeted therapy.

• Animals
• Apoptosis
• Carcinoma, Squamous Cell/genetics
• Carcinoma, Squamous Cell/pathology
• Cell Line, Tumor
• Cell Proliferation
• Head and Neck Neoplasms/genetics
• Head and Neck Neoplasms/pathology
• Humans
• Male
• Mice
• Mice, Nude
• MicroRNAs/genetics
• Molecular Chaperones/genetics
• Neoplasm Transplantation
• Polycomb Repressive Complex 1/genetics
• RNA-Binding Proteins/genetics
• Repressor Proteins/genetics
• bcl-2-Associated X Protein/genetics

• P20 CA192989 NCI NIH HHS
• 2G12RR003048 NCRR NIH HHS
• G12 MD007597 NIMHD NIH HHS
• G12 RR003048 NCRR NIH HHS
• CA192989-01 NCI NIH HHS
• P20 CA118770 NCI NIH HHS

microRNAs have been shown to play critical roles in regulating the chemosensitivity of cancer cells. As a member of the oncogenic miRNAs (oncomiRs), miR-222 has been reported to drive the oncogenesis of many types of malignancies. However, little is known concerning the specific role of miR-222 in human oral squamous cell carcinoma (OSCC). The present study explored the role and mechanism of miR-222 in increasing the expression of p53 up-regulated modulator of apoptosis (PUMA) and enhancing the sensitivity of OSCC to cisplatin (CDDP). Results showed that antisense (As)-miR-222 inhibits the expression of miR-222. In contrast, PUMA was dramaticallyup-regulated. IC₅₀ values were significantly decreased in cells treated with As-miR-222 combined with CDDP, to a greater extent than in cells treated with CDDP alone. Furthermore, As-miR-222 enhanced apoptosis and inhibited the invasiveness of UM1 cells. Analysis of the above data suggested that, in UM1 cells, there might be a regulatory loop between miR-222 and PUMA, and that miR-222 inhibition increased the chemosensitivity to CDDP. These findings demonstrated that down-regulation of miR-222 could enhance the chemosensitivity of human OSCC cells to CDDP, and that the combination of As-miR-222 and CDDP could be an effective therapeutic strategy by boosting the expression of PUMA for controlling the growth of OSCC.

• head and neck squamous cell carcinoma
• human papilloma virus
• miRNA
• oral and oropharyngeal cancers
• viral oncoprotein E6
• viral oncoprotein E7

Breast milk contains complex nutrients and facilitates the maturation of various biological systems in infants. Exosomes, membranous vesicles of endocytic origin found in different body fluids such as milk, can mediate intercellular communication. We hypothesized that microRNAs (miRNAs), a class of non-coding small RNAs of 18–25 nt which are known to be packaged in exosomes of human, bovine and porcine milk, may play important roles in the development of piglets.

In this study, exosomes of approximately 100 nm in diameter were isolated from porcine milk through serial centrifugation and ultracentrifugation procedures. Total RNA was extracted from exosomes, and 5S ribosomal RNA was found to be the major RNA component. Solexa sequencing showed a total of 491 miRNAs, including 176 known miRNAs and 315 novel mature miRNAs (representing 366 pre-miRNAs), which were distributed among 30 clusters and 35 families, and two predicted novel miRNAs were verified targeting 3’UTR of IGF-1R by luciferase assay. Interestingly, we observed that three miRNAs (ssc-let-7e, ssc-miR-27a, and ssc-miR-30a) could be generated from miRNA-offset RNAs (moRNAs). The top 10 miRNAs accounted for 74.5% (67,154 counts) of total counts, which were predicted to target 2,333 genes by RNAhybrid software. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses using DAVID bioinformatics resources indicated that the identified miRNAs targeted genes enriched in transcription, immunity and metabolism processes, and 14 of the top 20 miRNAs possibly participate in regulation of the IgA immune network.

Our findings suggest that porcine milk exosomes contain a large number of miRNAs, which potentially play an important role in information transfer from sow milk to piglets. The predicted miRNAs of porcine milk exosomes in this study provide a basis for future biochemical and biophysical function studies.

The online version of this article (doi:10.1186/1471-2164-15-100) contains supplementary material, which is available to authorized users.

Current evidence implicates aberrant microRNA expression patterns in human malignancies; measurement of microRNA expression may have diagnostic and prognostic applications. Roles for microRNAs in head and neck squamous cell carcinomas (HNSCC) are largely unknown. HNSCC, a smoking-related cancer, is one of the most common malignancies worldwide but reliable diagnostic and prognostic markers have not been discovered so far. Some studies have evaluated the potential use of microRNA as biomarkers with clinical application in HNSCC.

MicroRNA expression profile of oral squamous cell carcinoma samples was determined by means of DNA microarrays. We also performed gain-of-function assays for two differentially expressed microRNA using two squamous cell carcinoma cell lines and normal oral keratinocytes. The effect of the over-expression of these molecules was evaluated by means of global gene expression profiling and cell proliferation assessment.

Altered microRNA expression was detected for a total of 72 microRNAs. Among these we found well studied molecules, such as the miR-17-92 cluster, comprising potent oncogenic microRNA, and miR-34, recently found to interact with p53. HOX-cluster embedded miR-196a/b and miR-10b were up- and down-regulated, respectively, in tumor samples. Since validated HOX gene targets for these microRNAs are not consistently deregulated in HNSCC, we performed gain-of-function experiments, in an attempt to outline their possible role. Our results suggest that both molecules interfere in cell proliferation through distinct processes, possibly targeting a small set of genes involved in cell cycle progression.

Functional data on miRNAs in HNSCC is still scarce. Our data corroborate current literature and brings new insights into the role of microRNAs in HNSCC. We also show that miR-196a and miR-10b, not previously associated with HNSCC, may play an oncogenic role in this disease through the deregulation of cell proliferation. The study of microRNA alterations in HNSCC is an essential step to the mechanistic understanding of tumor formation and could lead to the discovery of clinically relevant biomarkers.

The implication of post-transcriptional regulation by microRNAs in molecular mechanisms underlying cancer disease is well documented. However, their interference at the cellular level is not fully explored. Functional in vitro studies are fundamental for the comprehension of their role; nevertheless results are highly dependable on the adopted cellular model. Next generation small RNA transcriptomic sequencing data of a tumor cell line and keratinocytes derived from primary culture was generated in order to characterize the microRNA content of these systems, thus helping in their understanding. Both constitute cell models for functional studies of microRNAs in head and neck squamous cell carcinoma (HNSCC), a smoking-related cancer. Known microRNAs were quantified and analyzed in the context of gene regulation. New microRNAs were investigated using similarity and structural search, ab initio classification, and prediction of the location of mature microRNAs within would-be precursor sequences. Results were compared with small RNA transcriptomic sequences from HNSCC samples in order to access the applicability of these cell models for cancer phenotype comprehension and for novel molecule discovery.

Ten miRNAs represented over 70% of the mature molecules present in each of the cell types. The most expressed molecules were miR-21, miR-24 and miR-205, Accordingly; miR-21 and miR-205 have been previously shown to play a role in epithelial cell biology. Although miR-21 has been implicated in cancer development, and evaluated as a biomarker in HNSCC progression, no significant expression differences were seen between cell types. We demonstrate that differentially expressed mature miRNAs target cell differentiation and apoptosis related biological processes, indicating that they might represent, with acceptable accuracy, the genetic context from which they derive. Most miRNAs identified in the cancer cell line and in keratinocytes were present in tumor samples and cancer-free samples, respectively, with miR-21, miR-24 and miR-205 still among the most prevalent molecules at all instances. Thirteen miRNA-like structures, containing reads identified by the deep sequencing, were predicted from putative miRNA precursor sequences. Strong evidences suggest that one of them could be a new miRNA. This molecule was mostly expressed in the tumor cell line and HNSCC samples indicating a possible biological function in cancer.

Critical biological features of cells must be fully understood before they can be chosen as models for functional studies. Expression levels of miRNAs relate to cell type and tissue context. This study provides insights on miRNA content of two cell models used for cancer research. Pathways commonly deregulated in HNSCC might be targeted by most expressed and also by differentially expressed miRNAs. Results indicate that the use of cell models for cancer research demands careful assessment of underlying molecular characteristics for proper data interpretation. Additionally, one new miRNA-like molecule with a potential role in cancer was identified in the cell lines and clinical samples.

• DNA methylation
• Gene profiling
• Genetic alterations
• Oncogenes
• Tumor suppressor genes
• miRNAs

• ZIA DC000073 Intramural NIH HHS
• ZIA DC000073-06 Intramural NIH HHS
• ZIA DC000074 Intramural NIH HHS
• ZIA DC000074-06 Intramural NIH HHS

Salivary adenoid cystic carcinoma (ACC) is a rare relentlessly progressive malignant tumor. The molecular events associated with ACC tumorigenesis are poorly understood. Variable microRNAs (miRNA) have been correlated with tumorigenesis of several solid tumors but not in ACC. To investigate the association of miRNAs with the development and/or progression of ACC, we performed a comparative analysis of primary ACC specimens and matched normal samples and a pooled salivary gland standard and correlated the results with clinicopathologic factors and validated selected miRNAs in a separate set of 30 tumors.

MiRNA array platform was used for the identification of target miRNAs and the data was subjected to informatics and statistical interrelations. The results were also collected with the MYB-NFIB fusion status and the clinicopathologic features.

Differentially dysregulated miRNAs in ACC were characterized in comparison to normal expression. No significant differences in miRNA expression were found between the MYB-NFIB fusion positive and -negative ACCs. Of the highly dysregulated miRNA in ACC, overexpression of the miR-17 and miR-20a were significantly associated with poor outcome in the screening and validation sets.

Our study indicates that the upregulation of miR-17-92 may play a role in the biology of ACC and could be potentially targeted in future therapeutic studies.

• Carcinogenesis/genetics
• Carcinoma, Adenoid Cystic/diagnosis
• Carcinoma, Adenoid Cystic/genetics
• Carcinoma, Adenoid Cystic/pathology
• Female
• Gene Expression Profiling
• Gene Fusion
• Genes, myb/genetics
• Humans
• Male
• MicroRNAs/genetics
• Middle Aged
• NFI Transcription Factors/genetics
• Oligonucleotide Array Sequence Analysis
• Prognosis
• RNA, Long Noncoding
• Reproducibility of Results
• Salivary Gland Neoplasms/diagnosis
• Salivary Gland Neoplasms/genetics
• Salivary Gland Neoplasms/pathology
• Survival Analysis
• Up-Regulation

• CA-16672 NCI NIH HHS
• P50 CA097007 NCI NIH HHS
• U01DE019765 NIDCR NIH HHS
• P30 CA016672 NCI NIH HHS
• U01 DE019765 NIDCR NIH HHS

• Cervical cancer
• HPV
• head-and-neck cancer
• messenger RNA profiling
• miRNA.

• IRS-1
• carcinoma
• miR-370
• mouth

Despite recent advancements in multidisciplinary treatments, the overall survival and quality of life of patients with advanced head and neck squamous cell carcinoma (HNSCC) have not improved significantly over the past decade. Molecular targeted therapies, which have been addressed and advanced by the concept of “oncogene addiction”, have demonstrated only limited successes so far. To explore a novel clue for clinically effective targeted therapies, we analyzed the molecular circuitry of HNSCC through the lens that HNSCC is an evolving system. In the trajectory of this somatic evolution, HNSCC acquires biological robustness under a variety of selective pressures including genetic, epigenetic, micro‐environmental and metabolic stressors, which well explains the major mechanism of “escaping from oncogene addiction”. On the other hand, this systemic view appears to instruct us approaches to target latent vulnerability of HNSCC that is masked behind the plasticity and evolvability of this complex adaptive system.

►

There is an urgent need to develop a novel conceptual framework for the treatment of HNSCC.

• microrna
• mir-218
• tumor suppressor
• focal adhesion
• laminin-332
• head and neck squamous cell carcinoma

• Carcinoma, Squamous Cell/genetics
• Carcinoma, Squamous Cell/metabolism
• Carcinoma, Squamous Cell/pathology
• Cell Adhesion Molecules/biosynthesis
• Cell Adhesion Molecules/deficiency
• Cell Adhesion Molecules/genetics
• Cell Growth Processes/genetics
• Cell Line, Tumor
• Cell Movement/genetics
• Gene Expression Regulation, Neoplastic
• Gene Knockdown Techniques
• Gene Silencing
• Head and Neck Neoplasms/genetics
• Head and Neck Neoplasms/metabolism
• Head and Neck Neoplasms/pathology
• Humans
• MicroRNAs/administration & dosage
• MicroRNAs/biosynthesis
• MicroRNAs/genetics
• Neoplasm Invasiveness
• RNA, Messenger/biosynthesis
• RNA, Messenger/genetics
• RNA, Small Interfering/administration & dosage
• RNA, Small Interfering/genetics
• Squamous Cell Carcinoma of Head and Neck
• Transfection
• Kalinin

• Biomarkers, Tumor/genetics
• Carcinoma, Squamous Cell/genetics
• Case-Control Studies
• Cell Line, Tumor
• DNA Methylation
• Gene Expression Profiling
• Humans
• Laryngeal Neoplasms/genetics
• MicroRNAs/genetics
• Mouth Neoplasms/genetics
• Oropharyngeal Neoplasms/genetics
• Polymerase Chain Reaction
• Sensitivity and Specificity

• P30 CA046934 NCI NIH HHS
• R01 DE021788 NIDCR NIH HHS
• R01 DE021788-01 NIDCR NIH HHS
• R01 DE021788-02 NIDCR NIH HHS

Based on the microRNA (miRNA) expression signatures of hypopharyngeal and esophageal squamous cell carcinoma, we found that miR-1 was significantly down-regulated in cancer cells. In this study, we investigated the functional significance of miR-1 in head and neck squamous cell carcinoma (HNSCC) cells and identified miR-1-regulated novel cancer pathways. Gain-of-function studies using miR-1 revealed significant decreases in HNSCC cell proliferation, invasion, and migration. In addition, the promotion of cell apoptosis and cell cycle arrest was demonstrated following miR-1 transfection of cancer cells. A search for the targets of miR-1 revealed that transgelin 2 (TAGLN2) was directly regulated by miR-1. Silencing of TAGLN2 significantly inhibited cell proliferation and invasion in HNSCC cells. Down-regulation of miR-1 and up-regulation of TAGLN2 were confirmed in HNSCC clinical specimens. Our data indicate that TAGLN2 may have an oncogenic function and may be regulated by miR-1, a tumor suppressive miRNA in HNSCC. The identification of novel miR-1-regulated cancer pathways could provide new insights into potential molecular mechanisms of HNSCC carcinogenesis.

MicroRNAs have emerged as important regulators of cell proliferation, development, cancer formation, stress responses, cell death, and other physiological conditions in the past decade. On the other hand, head and neck cancer is one of the top ten most common cancers worldwide. Recent advances in microRNAs have revealed their prominent role in regulating gene expression and provided new aspects of applications in diagnosis, prognosis, and therapeutic strategies in head and neck squamous carcinoma. In the present paper, we focus on microRNAs showing significant differences between normal and tumor cells or between cells with differential ability of metastasis. We also emphasize specific microRNAs that could modulate tumor cell properties, such as apoptosis, metastasis, and proliferation. These microRNAs possess the potential to be applied on clinical therapy in the future.

• blood
• mirnas
• mir-16
• mir-103
• ftd
• pgrn

• Cell Line, Tumor
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic
• Humans
• Intercellular Signaling Peptides and Proteins/genetics
• Male
• MicroRNAs/genetics
• Neoplasms/genetics
• Neoplasms/pathology
• Oligonucleotide Array Sequence Analysis
• Progranulins
• Prostatic Neoplasms/genetics
• Prostatic Neoplasms/pathology

• K08 NS050110 NINDS NIH HHS
• R01GM089784 NIGMS NIH HHS
• R01 NS061933 NINDS NIH HHS
• P30-AG028383 NIA NIH HHS
• R21 AG036875 NIA NIH HHS
• P30 AG028383 NIA NIH HHS
• R01 GM089784 NIGMS NIH HHS