Subsite-based alterations in miR-21, miR-125b, and miR-203 in squamous cell carcinoma of the oral cavity and correlation to important target proteins

Boldrup, Linda; Coates, Philip J.; Wahlgren, Magnus; Laurell, Göran; Nylander, Karin

doi:10.4103/1477-3163.104007

Cited by 46 publications

(44 citation statements)

References 41 publications

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“…miR-21 was found to be statistically significantly elevated in all peritumoral tissues compared to 3-cm distant mucosa. Previous studies have already proven the role of miR-21 in the modified regulation of p53-dependent apoptosis and cellcyle arrest in oral squamo-cellular carcinomas (17)(18)(19)(20)(21)(22). In our study, miR-21 showed a significantly elevated expression rate in meso-and hypopharyngeal carcinomas.…”

Section: Discussionsupporting

confidence: 61%

Comparative miRNA Expression Profile Analysis of Squamous Cell Carcinoma and Peritumoral Mucosa from the Meso- and Hypopharynx

Orosz

Gombos

Riedling³

et al. 2017

CGP

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Abstract. Background In Europe, according to the age-standardized rates per 100,000 population, Hungary had the highest estimated incidence, mortality and prevalence in lip, oral cavity and pharyngeal cancers for both sexes. Based on the cancer registerty held by the National Institute of Oncology, in 2010 and 2011 meso-and hypopharyngeal carcinomas counted more than 1,200 cases. The number of diagnosed mesopharyngeal carcinomas in our clinical site has doubled, while hypopharyngeal carcinoma cases have tripled since 1983 (Figures 1 and 2). Incidence of meso-and hypopharyngeal carcinomas is constantly growing, while the rate of mortality is above 50% due to late-stage recognition. In our clinical practice, malignant cancers of the meso-and hypopharyngeal regions are most specific in the 55-60 age range population, although the appearance of the different pharyngeal carcinomas has been observed in a growing number at younger ages in the past few years. It is important to note that the cancers affecting only one region, having good operability options and a better prognosis are disappearing, while the ones involving more than one region, with aggressive spreading and progressive prognosis are becoming more frequent. Our goal was to find and study a molecular marker that could be used as a predictive and a prognostic tool to complete clinical diagnostics.In recent years micro-RNAs (miRNA) have been excessively studied. These small, 19-25 base-pair-long RNAs are transcribed from an intra-or intergenic segment of DNA and are not translated into proteins. Matured miRNA binds to a ribonucleotid complex, called RISC (RNA induced silencing complex), and drives the regulation of mRNA translation, either by binding to the target mRNA's 3' UTR (untranslated region) segment, or to 5' UTR or just directly to the ORF (open reading frame). This way translation is blocked or endonucleases are activated causing the degradation of mRNA target (1, 2). An estimated 50-60% of the human genome is regulated by miRNAs. A specific mRNA can be regulated by multiple miRNAs, and a miRNA can modulate translation of more then hundred mRNAs (1). This RNA interference mechanism establishes precise modulation of gene expression, harmonic regulation of cellular functions as cell division, differentiation, apoptosis and intermediary metabolism (3). miRNAs can behave either as oncogenes (oncomirs) or tumor suppressors according to which target mRNA is regulated by them (1). miRNAs can be detected in blood serum, saliva and other body fluids (4-285

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Section: Discussionsupporting

confidence: 61%

Comparative miRNA Expression Profile Analysis of Squamous Cell Carcinoma and Peritumoral Mucosa from the Meso- and Hypopharynx

Orosz

Gombos

Riedling³

et al. 2017

CGP

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“…Moreover, miR-125b has been found to be dysregulated in ovarian cancer [37], breast cancer [38], and prostate cancer [39]. In OSCC, miR-125b also has been found to be downregulated [13] and showed a significant negative correlation with TP53 [40]. These data are in accordance with our results showing that an increased expression of mir-218, let-7g, and mir-125b predicts disease-free and disease-specific survival in OSCC patients (Figure 3).…”

Section: Discussionmentioning

confidence: 99%

MicroRNAs MiR-218, MiR-125b, and Let-7g Predict Prognosis in Patients with Oral Cavity Squamous Cell Carcinoma

et al. 2014

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MicroRNAs (miRNAs) have a major impact on regulatory networks in human carcinogenesis. In this study, we sought to investigate the prognostic significance of miRNAs in patients with oral cavity squamous cell carcinoma (OSCC). In a discovery phase, RNA was extracted from 58 OSCC tumor samples and paired normal tissues. MiRNAs expression was evaluated with TaqMan Array Card and TaqMan MicroRNA assays. The prognostic significance of the miRNA signature identified in the discovery phase was validated by qRT-PCR in a replication set consisting of 141 formalin-fixed, paraffin-embedded (FFPE) samples. We identified a miRNA regulatory network centered on the three hub genes (SP1, MYC, and TP53) that predicted distinct clinical endpoints. Three miRNAs (miR-218, miR-125b, and let-7g) and their downstream response genes had a concordant prognostic significance on disease-free survival and disease-specific survival rates. In addition, patients with a reduced expression of miR-218, miR-125b, and let-7g have a higher risk of poor outcomes in presence of specific risk factors (p-stage III-IV, pT3-4, or pN+). Our findings indicate that specific miRNAs have prognostic significance in OSCC patients and may improve prognostic stratification over traditional risk factors.

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“…While these studies included tissue collected from oral mucosa from different sites, tongue, gingiva and floor of the mouth [9–11] we here analyzed tissue from mobile tongue only.…”

Section: Discussionmentioning

confidence: 99%

Gene expression changes in tumor free tongue tissue adjacent to tongue squamous cell carcinoma

Boldrup

Coates

et al. 2016

Oncotarget

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Due to the high frequency of loco-regional recurrences, which could be explained by changes in the field surrounding the tumor, patients with squamous cell carcinoma of head and neck show poor survival. Here we identified a total of 554 genes as dysregulated in clinically tumor free tongue tissue in patients with tongue tumors when compared to healthy control tongue tissue. Among the top dysregulated genes when comparing control and tumor free tissue were those involved in apoptosis (CIDEC, MUC1, ZBTB16, PRNP, ECT2), immune response (IFI27) and differentiation (KRT36). Data suggest that these are important findings which can aid in earlier diagnosis of tumor development, a relapse or a novel squamous cell carcinoma of the tongue, in the absence of histological signs of a tumor.

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Subsite-based alterations in miR-21, miR-125b, and miR-203 in squamous cell carcinoma of the oral cavity and correlation to important target proteins

Cited by 46 publications

References 41 publications

Comparative miRNA Expression Profile Analysis of Squamous Cell Carcinoma and Peritumoral Mucosa from the Meso- and Hypopharynx

Comparative miRNA Expression Profile Analysis of Squamous Cell Carcinoma and Peritumoral Mucosa from the Meso- and Hypopharynx

MicroRNAs MiR-218, MiR-125b, and Let-7g Predict Prognosis in Patients with Oral Cavity Squamous Cell Carcinoma

Gene expression changes in tumor free tongue tissue adjacent to tongue squamous cell carcinoma

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