The Biological Role Of MiR-133a In MGC-803 And Its Mechanism

China is one of the countries which have high incidence of gastric cancer in the world.There are more than millions of new cases every year in the world and 41% of them happens in China.800,000 people die of gastric cancer each year and China accounts for 35% of them.Micro RNAs(mi RNAs)are small non-coding RNAs with 19~24 nucleotides.They negatively regulate gene expression through basic pairing with the 3' untranslated region(3'UTR)of target m RNAs,which results in m RNA degradation and/or translation repression.Through this biological role,mi RNAs have involed in physiological processes such as cell proliferation,differentiation,apoptpsis and metabolism.Abundant evidence implicates mi RNAs may function as oncogenes or tumor suppressors involved in tumor development.Some mi RNAs through negative regulation of tumor suppressor genes promote tumor occurrence and development,such as mi R-17-92,these mi RNAs may be viewed as "oncogenes";and others by inhibiting oncogenes to stop tumor development such as let-7,are regarded as "tumor suppressor genes".Ectopic expression of mi RNAs are related to tumor occurrence,and cancer progression.Abundant evidence implicates mi RNAs are involved in gastric cancer,liver cancer,lung cancer,breast cancer and other malignant tumors.Objective: To investigate the biological function and mechanism of mi R-133 a in gastric cancer(GC)cell line MGC-803.Methods:Real-time quantitative reverse transcriptase polymerase chain(q RT-PCR)was used to examine the expression levels of mi R-133 a in human GC and adjacent non-tumor tissues,as well as in GC cell lines(BGC-823,MGC-803,and AGS)and a human gastric mucosal epithelial cell line(GES-1).The biological role of mi RNA(mi R)-133 a was assessed in the GC cell line MGC-803 using MTT,apoptosis,migration and invasion assays.q RT-PCR and western blot analyses were used to evaluate the potential target gene expression of mi R-133 a.The regulation of IGF1 R by mi R-133 a was verified using the luciferase reporter assay.Results: In 80% of the 105 GC patients,the mean expression of mi R-133 a was significantly downregulated in tumor tissues compared with adjacent normal tissues.Compared with a control construct,forced expression of mi R-133 a in GC cell line MGC-803 inhibited proliferation(0.5448 ± 0.0085 vs 0.7270 ± 0.0084,P = 0.001);migration 0.6126 ± 0.0311 vs 1.024 ± 0.0456,P = 0.0017);and invasion(0.7433 ± 0.0221 vs 1.017 ± 0.0311,P = 0.002).It also induced apoptosis(22.69% ± 0.7846% vs 9.347% ± 0.3012%,P < 0.0001).In addition,we identified IGF1 R as a regulatory target of mi R-133 a in GC.Conclusions: This study suggests that mi R-133 a is downregulated in GC cell lines and functions as a tumor suppressor in vivo directly by repressing IGF1R.