MicroRNA expression profile in head and neck cancer: HOX-cluster embedded microRNA-196a and microRNA-10b dysregulation implicated in cell proliferation

Abstract

BackgroundCurrent 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.MethodsMicroRNA 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.ResultsAltered 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.ConclusionsFunctional 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.

A Minimal DNA Methylation Signature in Oral Tongue Squamous Cell Carcinoma Links Altered Methylation with Tumor Attributes

“…Unlike in some cancers, its role in HNSCC is unclear (63). We found a large functional hypermethylated DMR around miR-10B spanning several megabases ( Fig.…”

Association of miR-193b Down-regulation and miR-196a up-Regulation with Clinicopathological Features and Prognosis in Gastric Cancer

“…miR-196a is a known onco-miRNA that plays an important role in tumorigenesis and tumor progression (Peng et al, 2010;Sun et al, 2012). Emerging evidence suggests the aberrant over-expression of miR-196a is a frequent event in various cancers, including head and neck squamous cell carcinomas (Severino et al, 2013), laryngeal cancer (Saito et al, 2013), pancreatic cancer (Liu et al, 2013), and gastric cancer (Tsai et al, 2012). It has been reported that over-expression of miR-196a is associated with apoptosis, invasion, and proliferation in pancreatic cancer (Liu et al, 2013).…”

MicroRNA‐196a promotes an oncogenic effect in head and neck cancer cells by suppressing annexin A1 and enhancing radioresistance

“…The first identified targets of miR‐196a were HOXA and HOXB genes in primary adult acute myeloid leukaemia, and HOXC8 and HOXB7 in malignant melanoma . However, HOX genes have not been shown to be regulated by miR‐196a in head and neck cancer cell lines such as SCC25 and FaDu . Other validated targets of miR‐196a include annexin A1 (ANXA1), S100A9, SPRR2C and KRT5 in oesophageal cancer cells, and ERG in leukaemia, but the precise roles of these targets in regulating the oncogenic effects of miR‐196a so far remain unclear.…”