Expression of TP53 mutation-associated microRNAs predicts clinical outcome in head and neck squamous cell carcinoma patients

Ganci, Federica; Sacconi, Andrea; Ben-Moshe, Noa Bossel; Manciocco, Valentina; Sperduti, Isabella; Strigari, Lidia; Covello, Renato; Benevolo, Maria; Pescarmona, Edoardo; Domany, Eytan; Muti, Paola; Strano, Sabrina; Spriano, Giuseppe; Fontemaggi, Giulia; Blandino, Giovanni

doi:10.1093/annonc/mdt380

Cited by 83 publications

(126 citation statements)

References 24 publications

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“…The present study analyzes miR-21-3p (miR-21*), which is known to also be up-regulated in cancer tissue, as notated by Lu et al [20]. miR-21-3p overexpression has also been determined elsewhere in a group of head and neck cancers [8]. While the sample size in present study may have been too small to determine any other correlations, other studies have also failed to describe any association between the expression profile of miR-21-5p and clinicopathological parameters in LSCC [12].…”

Section: Discussionmentioning

confidence: 85%

New miRNA expression abnormalities in laryngeal squamous cell carcinoma

Cybula

Wieteska

Józefowicz-Korczyńska

et al. 2016

CBM

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Abstract. BACKGROUND:Although the development of novel diagnostic and treatment strategies concerning laryngeal cancer is highly intensive, the survival rate remains virtually unchanged. Small non-coding RNAs appear to be very promising biomarkers -and so remain the focus of extensive investigation in laryngeal cancer. OBJECTIVE: We examined the expression of five miRNA and five genes related to cancer whether they could be potential laryngeal cancer biomarkers. METHODS:We performed an analysis in 47 patients diagnosed with laryngeal cancer. The qPCR technique was used to investigate the expression profile. RESULTS: While miR-21-3p and miR-525-5p were found to be significantly up-regulated, miR-139-3p and miR-885-5p expression is lower in laryngeal cancer. Moreover, PIK3R1 and HACE1 were found to be also down-regulated. CONCLUSIONS: The change in miRNA expression is frequent than the expression of other tested genes. The expression of passenger strands such as miR-21-3p and miR-139-3p, which are rarely investigated, is also significantly affected in laryngeal cancer. While PIK3R1, HACE1, miR-139-3p, and miR-885-5p may act as tumor suppressor genes in the studied tumour type, miR-21-3p and miR-525-5p seem to have oncogenic properties. Our findings suggest that miR-885-5p and PIK3R1 are the best indicators for the classification of laryngeal cancer tissue and normal mucosa.

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Section: Discussionmentioning

confidence: 85%

New miRNA expression abnormalities in laryngeal squamous cell carcinoma

Cybula

Wieteska

Józefowicz-Korczyńska

et al. 2016

CBM

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“…p53 plays a crucial role in cell cycle regulation and apoptosis and it is the most commonly mutated gene in HNSCC [45][46][47]. The expression of TP53 mutation-associated miRNAs has been linked to survival in HNSCC [48]. miR-31 (upregulated in HNSCC) has been shown to affect the activation of the transcription factor, hypoxia-inducible factor (HIF) under normoxic conditions contributing to the development of HNSCC [49].…”

Section: Transcription Factorsmentioning

confidence: 99%

MicroRNAs and head and neck cancer: Reviewing the first decade of research

Sethi¹,

Wright²,

Wood³

et al. 2014

European Journal of Cancer

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“…These samples belong to the cohort previously described by Ganci and colleagues, where TP53 status was assessed by direct sequencing of exons 2 through 11 [45, 46]. In HNSCCs TP53 mutation is a very frequent event and in our series its incidence is nearly 58%.…”

Section: Resultsmentioning

confidence: 99%

Gain of function mutant p53 proteins cooperate with E2F4 to transcriptionally downregulate RAD17 and BRCA1 gene expression

Valenti¹,

Ganci²,

Fontemaggi³

et al. 2015

Oncotarget

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Genomic instability (IN) is a common feature of many human cancers. The TP53 tumour suppressor gene is mutated in approximately half of human cancers. Here, we show that BRCA1 and RAD17 genes, whose derived proteins play a pivotal role in DNA damage repair, are transcriptional targets of gain-of-function mutant p53 proteins. Indeed, high levels of mutp53 protein facilitate DNA damage accumulation and severely impair BRCA1 and RAD17 expression in proliferating cancer cells. The recruitment of mutp53/E2F4 complex onto specific regions of BRCA1 and RAD17 promoters leads to the inhibition of their expression. BRCA1 and RAD17 mRNA expression is reduced in HNSCC patients carrying TP53 mutations when compared to those bearing wt-p53 gene. Furthermore, the analysis of gene expression databases for breast cancer patients reveals that low expression of DNA repair genes correlates significantly with reduced relapse free survival of patients carrying TP53 gene mutations. Collectively, these findings highlight the direct involvement of transcriptionally active gain of function mutant p53 proteins in genomic instability through the impairment of DNA repair mechanisms.

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Expression of TP53 mutation-associated microRNAs predicts clinical outcome in head and neck squamous cell carcinoma patients

Cited by 83 publications

References 24 publications

New miRNA expression abnormalities in laryngeal squamous cell carcinoma

New miRNA expression abnormalities in laryngeal squamous cell carcinoma

MicroRNAs and head and neck cancer: Reviewing the first decade of research

Gain of function mutant p53 proteins cooperate with E2F4 to transcriptionally downregulate RAD17 and BRCA1 gene expression

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