Role of microRNA-296-3p in the malignant transformation of sinonasal inverted papilloma

Kakizaki,Tomohiko; Hatakeyama,Hiromitsu; Nakamaru,Yuji; Takagi,Dai; Mizumachi,Takatsugu; Sakashita,Tomohiro; Kano,Satoshi; Homma,Akihiro; Fukuda,Satoshi

doi:10.3892/ol.2017.6193

Role of microRNA-296-3p in the malignant transformation of sinonasal inverted papilloma

Authors:
- Tomohiko Kakizaki
- Hiromitsu Hatakeyama
- Yuji Nakamaru
- Dai Takagi
- Takatsugu Mizumachi
- Tomohiro Sakashita
- Satoshi Kano
- Akihiro Homma
- Satoshi Fukuda
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Affiliations: Department of Otolaryngology‑Head and Neck Surgery, Hokkaido University Graduate School of Medicine, Sapporo 060‑8638, Japan
Published online on: May 17, 2017 https://doi.org/10.3892/ol.2017.6193
Pages: 987-992

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Abstract

Inverted papilloma (IP) is a benign tumor occurring in the nasal cavity and paranasal sinuses. It is reported that 5-15% of IPs undergo malignant transformation into squamous cell carcinoma (SCC), and the role of microRNAs (miRNA/miR) in this process remains to be elucidated. In the present study, whole miRNA profiles using samples of IP and SCC were investigated, in order to detect the function of miRNA in the carcinogenesis of IP. Samples from IPs (n=5) and SCC lesions (n=5), which arose from IPs, were used for miRNA analysis. A total of 200 miRNAs exhibited a >2‑fold differential expression between IP and SCC. miR‑296‑3p was markedly upregulated in SCC with a 23‑fold difference. Computational analysis indicated that miR‑296‑3p targeted PTEN, which regulates the phosphoinositide 3‑kinase (PI3K)/protein kinase B (Akt) signaling pathway and PTEN is involved in the carcinogenesis of SCC. miR‑296‑3p directly regulated PTEN expression in head and neck cancer cells, with PTEN protein levels decreased in 4/19 the SCCs (21.0%), as compared with those in the IPs (76.4%). Positive p21 staining was observed in 64.7% of IPs; this was a significantly increased rate compared with that for SCCs (26.3%, P=0.0086). The results of the present study indicated that there were marked changes in the miRNA expression signature during the malignant transition. miR‑296‑3p may serve an important role in the malignant transformation of IPs via the regulation of PTEN, combined with the subsequent inhibition of the PI3K/Akt signaling pathway, and may be a novel agent for cancer prevention.

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