Kakizaki Tomohiko, Hatakeyama Hiromitsu, Nakamaru Yuji, Takagi Dai, Mizumachi Takatsugu, Sakashita Tomohiro, Kano Satoshi, Homma Akihiro, Fukuda Satoshi
Department of Otolaryngology-Head and Neck Surgery, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.
Oncol Lett. 2017 Jul;14(1):987-992. doi: 10.3892/ol.2017.6193. Epub 2017 May 17.
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.
内翻性乳头状瘤（IP）是一种发生于鼻腔和鼻窦的良性肿瘤。据报道，5%-15%的IP会恶变为鳞状细胞癌（SCC），而微小RNA（miRNA/miR）在此过程中的作用仍有待阐明。在本研究中，利用IP和SCC样本对整个miRNA谱进行了研究，以检测miRNA在IP癌变中的作用。来自IP（n=5）和由IP发生的SCC病变（n=5）的样本用于miRNA分析。共有200种miRNA在IP和SCC之间表现出>2倍的差异表达。miR-296-3p在SCC中显著上调，差异达23倍。计算分析表明，miR-296-3p靶向PTEN，PTEN可调节磷酸肌醇3激酶（PI3K）/蛋白激酶B（Akt）信号通路，且PTEN参与SCC的癌变过程。miR-296-3p直接调节头颈部癌细胞中PTEN的表达，与IP中的PTEN蛋白水平（76.4%）相比，4/19的SCC（21.0%）中PTEN蛋白水平降低。在64.7%的IP中观察到p21染色呈阳性；与SCC相比，这一比例显著升高（26.3%，P=0.0086）。本研究结果表明，在恶性转变过程中miRNA表达特征发生了显著变化。miR-296-3p可能通过调节PTEN，进而抑制PI3K/Akt信号通路，在IP的恶性转化中发挥重要作用，可能是一种新型的癌症预防药物。
