MicroRNA-145 inhibits growth of laryngeal squamous cell carcinoma by targeting the PI3K/Akt signaling pathway

Dong Ye,1,2 Chongchang Zhou,2 Hongxia Deng,2 Lexi Lin,2 Shuihong Zhou11Department of Otorhinolaryngology-Head and Neck Surgery, The First Affiliated Hospital of Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Otorhinolaryngology-Head and Neck Surgery, Lihuili Hospital of Ningbo University, Ningbo, Zhejiang, People’s Republic of ChinaPurpose: In this study, we used a nude mouse model of human laryngeal squamous cell carcinoma (LSCC) to investigate inhibition of tumor growth by microRNA-145 (miR-145) and the mechanisms underlying this inhibition.Methods: Tumors were established in nude mice by transplantation of the LSCC AMC-HN-8 cell line. Forty-eight nude mice were randomly divided into groups of eight mice each and treated with high (1.0 optical density [OD]) or low (0.5 OD) doses of miR-145, or relevant control treatments. Tumor growth was observed in each group and used to calculate the inhibition rate. Routine pathological and electron microscopic examinations were used to determine tumor apoptosis and proliferation. Changes in levels of miR-145 and PI3K and Akt protein levels were also analyzed.Results: MiR-145 inhibited LSCC growth in a dose-dependent manner, as tumor growth was significantly inhibited in mice injected intratumorally with high-dose miR-145 compared with both the untreated and low-dose miR-145 groups (p<0.05). Pathological examination showed increased tumor necrotic and apoptotic changes in treated mice, which was confirmed by electron microscopy. PI3K and Akt protein expression were significantly lower in tumors treated with high-dose miR-145 group compared with those in the untreated and low-dose miR-145 groups (p<0.05).Conclusions: MiR-145 was associated with inhibited tumor growth in a nude mouse model of LSCC. The underlying mechanism may be inhibition of the PI3K/Akt signaling pathway, which regulates tumor growth, invasion, and metastasis and also plays an important role in tumor angiogenesis and proliferation of tumor stem cells. MiR-145 may act as a tumor suppressor gene and is a promising candidate for cancer treatment.Keywords: laryngeal squamous cell carcinoma, animal model, miRNA-145, oncology, treatment, mechanis