The Role And Mechanism Of LncRNA MIAT On Proliferation,Invasion And Migration Of Colon Cancer

Colon cancer is one of the most serious digestive tract malignant tumors that threat to human health.The incidence and mortality of colon cancer increased each year due to the change of the dietary habits and lifestyle.The classic treatment of colon cancer was surgery combined with chemotherapy.In recent years,the survival rate of colon cancer was improved with the development of chemotherapy drugs.The 5-year survival rate of situ colon cancer patients was over 90%,while that of patients with lymph node metastasis or distant organ metastasis was less than 50%.The metastasis is the main cause of death in colon cancer patients.Therefore,revealing the molecular mechanism involved in the proliferation and metastasis of colon cancer is useful to a comprehensive prevention and treatment of colon cancer.Long non-coding RNAs(LncRNA)are defined as transcripts great than 200 nt without protein coding function.The aberrant LncRNA expression was involved in the development of many diseases.In recent years,LncRNA MIAT played an important role in cardiovascular disease,neuroendocrine prostate cancer and chronic lymphocytic leukemia.However,the role and mechanism of LncRNA MIAT in colon cancer remain largely unknown.In present study,we observed that the expression of LncRNA MIAT was significantly increased in colon cancer tissue and colon cancer cell line HT29,SW480 and LOVO cells.In addition,high expression of LncRNA MIAT was associated with TNM stage,tumor grade and tumor metastasis in patients with colon cancer.Down-regulation of LncRNA MIAT significantly inhibited proliferation and clone of colon cancer cells.Further study showed that deletion of LncRNA MIAT expression obviously increased apoptosis and decreased metastasis of colon cancer cells.Inhibition of LncRNA MIAT had no effect on cell cycle.There was a negative correlation between miR-132 level and LncRNA MIAT level in colon cancer tissues.Using RNA pull-down and RNA immunoprecipitation,we revealed that LncRNA MIAT could interact with miR-132.We also showed that Derlin-1 was the target molecule of miR-132 in colon cancer cells.MiR-132 mediated the promotion of apoptosis and the inhibition of invasion and migration in colon cancer cells.More important,LncRNA MIAT regulated the expression of Derlin-1.Interference of LncRNA MIAT significantly inhibited the growth of xenograft tumor in nude mice.In conclusion,the increased expression of LncRNA MIAT resulted in the decrease of miR-132 expression,leading to the elevation of Derlin-1 expression.Thus,it promoted proliferation and metastasis of colon cancer cells.Our study revealed the role and mechanism of LncRNA MIAT in colon cancer and prodided an effective target for the treatment of colon cancer.