Biological Behavior And Clinical Significance Of MiR-21 And Gastric Cancer Cells

Background:Gastric cancer(GC)is one of the most common malignant tumors in the digestive tract,and its morbidity and mortality rank fourth and second respectively in global malignancies.[1]In China,the annual incidence of new-onset gastric cancer is about 679,000,and the number of deaths due to gastric cancer is as high as 498,000 per year[2].Only about 10%of patients with gastric cancer were diagnosed at an early stage,and the best surgical treatment period has been missed.Chemotherapy is currently the main non-surgical treatment.The formation of chemotherapeutic drug resistance is the main reason for the poor efficacy of chemotherapy.Therefore,improving the sensitivity of gastric cancer cells to chemotherapy drugs and reducing their drug resistance have become the most important treatment for gastric cancer Paclitaxel(PTX)combined with chemotherapy as a common chemotherapy for gastric cancer is widely used in the treatment of gastric cancer,but because of its low sensitivity,more than 50%of gastric cancer patients can not benefit from paclitaxel chemotherapy[3].MicroRNA(miRNA)is a small non-coding ribonucleic acid,which is endogenous and highly conserved,and plays an important role in the process of gene translation and transcription[4].There are two ways to regulate miRNA:in some animals and plants,miRNA can bind to the 3'-untranslated region(3'-UTR)of the target gene mRNA to degrade the target gene mRNA,thereby reducing The expression of the target gene mRNA;in most animals,the 3'-UTR of the target gene mRNA complements the miRNA and reduces the expression of the target protein,thereby exerting a negative regulatory effect[5].miRNAs affect the biological behavior of a variety of malignant tumors,such as proliferation,apoptosis,invasion and migration of various tumor cells[6].Previous studies have found that high expression of miRNA-21 can inhibit the expression of PTEN and affect the PI3K/AKT pathway leading to drug resistance[71 The relationship between paclitaxel chemotherapy resistance and the expression level of miRNA-21 was not analyzed.Objective:The relative expression of miRNA-21 in gastric cancer tissues was examined,and its relationship with the biological behavior of gastric cancer cells was investigated.The relationship between the relative expression of miRNA-21 and the chemosensitivity of paclitaxel and the possible mechanism of drug resistance were investigated.Methods:Collecting specimens of 25 gastric cancer patients and adjacent tissues(>5.0 cm from cancer tissues)undergoing D2 radical resection of gastric cancer in the Department of Abdominal Surgery,Kunming University Third Affiliated Hospital from October 2016 to March 2017,the gastric cancer cells and RNA in the paracancerous tissues was extracted and reverse transcribed,and the expression of miR-21 in the collected samples was examined by real-time polymerase chain reaction(RT-qPCR).The clinical data of patients were collected to explore the relationship between the relative expression level of miRNA-21 and tumor pathology.The relationship between the relative expression of miRNA-21 and migration ability was studied by scratch test.The relative in vitro invasion of Transwell cells was used to verify the relative expression of miRNA-21.The relationship between expression level and invasive ability;the relationship between the expression level of miRNA-21 and proliferation ability was verified by MTT colorimetry;the relationship between the apoptosis ability of gastric cancer cells and the expression level of miRNA-21 by flow cytometry;CCK-8 detection of miRNA The effect of-21 on the half-inhibitory concentration of gastric cancer cells under different concentrations of paclitaxel;Relationship between expression of miR-21 and Bcl-2,Bax and PTEN in different expression levels of gastric cancer cells by Western Blot.Result:(1)The relative expression of miRNA-21 in gastric cancer tissues was over-expressed compared with adjacent normal tissues(P=0.015);(2)Compared with NC group,the proliferation ability of gastric cancer SGC-7901 cells transfected with miRNA-21 mimics(P=0.038),invasive ability(P=0.000),migration ability(P=0.021)enhanced,down-regulation of miRNA-21 expression level could promote gastric cancer cell apoptosis(P=0.000);(3)gastric cancer SGC-7901 cell NC group The IC50 of the miR-21 mimetic group and the miR-21 inhibitor group were(7.51±0.45),(3.98±0.24),(1.19±0.16),miR-21 mimetic group,miR-21 inhibitor group and NC.P<0.01 was compared between groups(4)PTEN(P=0.037)and Bax protein expression levels were higher in the miRNA-21 inhibitor group than in the NC group(P=0.039),while the protein level of Bcl-2 was decreased(P=0.000).Conclusion:1.The expression level of MiRNA-21 was higher in gastric cancer tissues than in adjacent tissues,and the positive rate of lymphatic metastasis was higher in gastric cancer patients with higher expression of miRNA-21,and the stage was later;2.High expression of MiRNA-21 up-regulates the proliferation,migration and invasion of gastric cancer cells and down-regulates the apoptosis ability of gastric cancer cells;3.Highly expressed MiRNA-21 gastric cancer cells may inhibit the apoptosis of gastric cancer cells by increasing the expression level of Bcl-2,thereby making gastric cancer resistant to paclitaxel chemotherapy.