Long Non-coding RNA＿GAS5 Regulates PI3K/AKT/mTOR Inhibits The Cell Proliferation And Invation Of Laryngeal Cancer Cells

BackgroundLaryngeal cancer is one of the common malignant tumors,and its incidence accounts for about 1%to 5%of systemic tumors.In recent years,the incidence of laryngeal cancer has increased,but the 5-year survival rate of laryngeal cancer patients has not shown an increasing trend in the past two decades.This may be because the occurrence and development of laryngeal cancer is a complex pathological process.All,the study of the specific molecular mechanism of laryngeal cancer has a crucial role in the diagnosis and treatment of laryngeal cancer.Growth arrest specific transcription factor 5(growth arrest Special5,GAS5)is a common long non-coding RNA((long non-coding RNA,lncRNA)).In recent years,many scholars have found that GAS5 is abnormally expressed in many tumors and plays an important role in tumor progression.However,its role and mechanism in laryngeal cancer are still unclear.PI3K/AKT/mTOR is one of the three main signaling pathways that have been determined to be important for cancer.This signaling pathway plays an important role in the self-renewal of cancer stem cells and resistance to chemotherapy or radiotherapy.The starbase database shows that GAS5 has a high correlation with PI3K/AKT/mTOR.It is not clear whether there is abnormal expression of GAS5 in laryngeal cancer cells and whether it produces functional changes through the PI3K/AKT/mTOR signaling pathway.This study intends to explore the role of GAS5 in the occurrence and development of laryngeal carcinoma and related mechanisms through the study of laryngeal carcinoma specimen tissues and laryngeal carcinoma cell lines.Objective1.Detect the differential expression of GAS5 in laryngeal carcinoma and adjacent tissues,and explore the correlation of its clinical characteristics;2.Detect the influence of GAS5 on the biological behaviors of laryngeal cancer cell proliferation,apoptosis,migration and invasion;3.Detect the influence of abnormal expression of GAS5 on PI3K/AKT/mTOR signaling pathway;Methods1.Collect 40 cases of laryngeal carcinoma and paracancerous tissues from the Department of Otorhinolaryngology Head and Neck Surgery,Guangdong Provincial People’s Hospital,and use Real-time fluorescent quantitative PCR detection of GAS5 differential expression and clinical characteristics analysis;2.GAS 5 was overexpressed in TU212 and TU686 laryngeal cancer cell lines,and the effects of GAS5 on the proliferation,apoptosis,migration and invasion of laryngeal cancer cells were detected by CCK-8,flow cytometry,Transwell experiments and animal experiments;3.Detect the expression changes of PTEN,P13K,Akt,p-Akt,mTOR and in TU212 and TU686 cell lines after overexpression of GAS5 by Western blot,and explore the mechanism of these protein’s changes.Results1.GAS5 is down-regulated in laryngeal cancer tissues,the lower its expression,the worse the tumor differentiation,the later the TMN staging,the higher the lymph node metastasis rate and the shorter the overall survival time.2.After overexpression of GAS5,the division of TU212 and TU686 laryngeal carcinoma cells was blocked in G2/M phase,the apoptosis rate increased,and the migration and invasion ability was inhibited.3.After overexpression of GAS5,the expression level of PTEN in TU212 and TU686 laryngeal cancer cells increased,while the expression levels of P13K,p-AKT and p-mTOR decreased.Conclusion1.The expression level of GAS 5 in laryngeal cancer tissue decreases,and its low expression is closely related to poor tumor differentiation,advanced TMN staging,lymph node metastasis and shorter overall survival time;2.GAS5 shows the function of inhibiting the proliferation of laryngeal cancer cells in vivo and in vitro,and may be a tumor suppressor gene in the development of laryngeal cancer;3.GAS5 may inhibit the proliferation and metastasis of laryngeal cancer cells through PI3K/AKT/mTOR signaling pathway.