MicroRNA expression as predictor of local recurrence risk in oral squamous cell carcinoma

Ganci, Federica; Sacconi, Andrea; Manciocco, Valentina; Sperduti, Isabella; Battaglia, Paolo; Covello, Renato; Muti, Paola; Strano, Sabrina; Spriano, Giuseppe; Fontemaggi, Giulia; Blandino, Giovanni

doi:10.1002/hed.23969

Cited by 50 publications

(46 citation statements)

References 41 publications

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“…Interestingly, high expression of four of these miRNAs (miR-96-5p, miR-21-3p, miR-21-5p, and miR-429) was previously shown to be predictive of recurrence in head and neck squamous cell carcinoma. 15,16 Expression of these four miRNAs in peritumors was intermediate to that of tumoral and normal tissues, except for miR-429, which showed similar expression levels in tumoral and peritumoral tissues (Supplementary Figure S1). Validation of altered expression level of these miRNAs between peritumoral and normal tissues was performed by RT-qPCR on a series of 132 peritumors and 18 normal tissues (Figure 2e).…”

Section: Histologically Tumor-free Peritumor Tissue From Head and Necmentioning

confidence: 99%

“…[12][13][14] In particular, our group together with others has observed a correlation between the expression of specific miRNAs and outcome of head and neck squamous cell carcinoma patients. 12,[14][15][16] Here, we aimed at identifying key alterations of miRNAs expression occurring in tumor-surrounding mucosa (referred to as 'peritumoral' mucosa hereafter) from head and neck squamous cell carcinoma patients, which predict local recurrence. In particular, the identification of a predictive miRNA signature in peritumoral tissues may have relevance for early detection of minimal residual disease and of pre-cancer molecular alterations implicated in malignant transformation.…”

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confidence: 99%

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Altered peritumoral microRNA expression predicts head and neck cancer patients with a high risk of recurrence

Ganci¹,

Sacconi²,

Manciocco³

et al. 2017

Modern Pathology

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Head and neck squamous cell carcinoma is typically characterized by a high incidence of local recurrences. It has been extensively shown that mucosa from head and neck squamous cell carcinoma patients carries both genetic and gene expression alterations, which are mostly attributable to major etiologic agents of head and neck squamous cell carcinoma. We previously identified a signature of microRNAs (miRNAs) whose high expression in tumors is predictive of recurrence. Here, we investigated whether the deregulation of miRNA expression in the tumor-surrounding mucosa is correlated to disease recurrence. Specifically, comparing the miRNA expression in matched tumoral, peritumoral, and normal tissues collected from head and neck squamous cell carcinoma patients, we identified 35 miRNAs that are deregulated in both tumoral and peritumoral tissues as compared with normal matched samples. Four of these composed a miRNA signature that predicts head and neck squamous cell carcinoma local recurrence independently from prognostic clinical variables. The predictive power of the miRNA signature increased when using the expression levels derived from both the peritumoral and the tumoral tissues. The expression signal of the miRNAs composing the predictive signature correlated with the transcriptional levels of genes mostly associated with proliferation. Our results show that expression of miRNAs in tumor-surrounding mucosa may strongly contribute to the identification of head and neck squamous cell carcinoma patients at high risk of local recurrence.

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Section: Histologically Tumor-free Peritumor Tissue From Head and Necmentioning

confidence: 99%

mentioning

confidence: 99%

Altered peritumoral microRNA expression predicts head and neck cancer patients with a high risk of recurrence

Ganci¹,

Sacconi²,

Manciocco³

et al. 2017

Modern Pathology

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“…Several aberrantly expressed miRNAs have been recognized in OSCC, especially in chemoresistant OSCC, suggesting their critical roles in tumorigenesis and cancer recurrence. Moreover, miRNAs have been reported to function as prognostic indicators for relapse in patients with OSCC . Among these miRNAs, let‐7 family members have been found to be dysregulated in a variety of cancers and widely viewed as tumor suppressors.…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, miRNAs have been reported to function as prognostic indicators for relapse in patients with OSCC. 9 Among these miRNAs, let-7 family members have been found to be dysregulated in a variety of cancers 10,11 and widely viewed as tumor suppressors. It has been shown that let-7…”

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confidence: 99%

Let‐7c restores radiosensitivity and chemosensitivity and impairs stemness in oral cancer cells through inhibiting interleukin‐8

Peng

Wang

Lee

et al. 2018

J Oral Pathology Medicine

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“…Many factors, such as arecoline, are oxidative inducers (3). The five-year survival of OSCC remained low and this malignancy tended to relapse after treatment (4). Therefore, it is important to specify the molecular dysregulation in the regulatory axis contributive to OSCC pathogenesis to develop therapeutic modalities (5).…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-211 Enhances the Oncogenicity of Carcinogen-Induced Oral Carcinoma by Repressing TCF12 and Increasing Antioxidant Activity

Chen¹,

et al. 2016

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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-EGFPmiR-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. Ó2016 AACR.

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MicroRNA expression as predictor of local recurrence risk in oral squamous cell carcinoma

Abstract: MiRNAs are differentially expressed in OSCC versus normal samples. The expression of 4 prognostic miRNA signatures is able to predict recurrence risk independently from other clinical factors in OSCC. © 2015 Wiley Periodicals, Inc. Head Neck 38: E189-E197, 2016.

Cited by 50 publications

References 41 publications

Altered peritumoral microRNA expression predicts head and neck cancer patients with a high risk of recurrence

Altered peritumoral microRNA expression predicts head and neck cancer patients with a high risk of recurrence

Let‐7c restores radiosensitivity and chemosensitivity and impairs stemness in oral cancer cells through inhibiting interleukin‐8

MicroRNA-211 Enhances the Oncogenicity of Carcinogen-Induced Oral Carcinoma by Repressing TCF12 and Increasing Antioxidant Activity

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