| Gastric cancer is a high incidence malignant tumor with worse prognosis. Therefore,this disease threats to human health seriously. As one of the most common malignant tumors in China, the mortality of gastric cancer ranks the third highest among all of malignant tumors. Most patients with gastric cancer were found at the advanced stages, which has brought great distress to the treatment and the patient's survival. The study on the occurrence and development of gastric cancer has been a hot research in the field of cancer research so far, however, but until today it has not yet established a complete set of theories, which makes our clinical treatment and early diagnosis have been hovering at a stage, and have not found the right breakthrough. Therefore, to improve the pathological mechanism and the progression hypothesis of gastric cancer is of great significance for the clinical diagnosis, treatment and prognosis in gastric cancer. Recent years, with the focus of the field of life sciences from proteomics to the focus on the transcriptomics, the lnc RNA is found to be an important factor in life adjustment and adaptation. Therefore, advancing the study of lnc RNA expression and function will help to further understand the pathogenesis and progression of human diseases, especially cancer.Objective: To detect and investigate the lnc RNA expression profile of gastric adenocarcinoma(GA), to analyze the correlation between lnc RNA expression levels and clinical pathological features of patients with GA, and to explore its function in GA cells.Methods:1. Using the lnc RNA microarray to detect and analyze the lnc RNA expression profile in 6 paired GA tissues.2. To preliminary verify the expression levels of lnc RNA CTC-425O23.2 in GA and their paired para-carcinoma tissues by using real time fluorescent quantitative reverse transcription PCR(q RT-PCR).3. Using si RNA silencing technique to preliminarily explore the function of lnc RNA CTC in GA cells by using MTT, scratch damage, Transwell and Flow cytometry assays.4. Applying bioinformatics to predict the possible molecular mechanisms of lnc RNA CTC in the occurrence and progression of GA.Results:1. The chip results showed that compared to the 6 paired para-carcinoma tissues,there were both about 1700 up-regulated and down-regulated lnc RNAs that had been detected in GA tissues. The abnormal expression of lnc RNAs are widely involved in the various biological process of cells, and play important roles in the occurrence and development of cancer. Lnc RNA CTC was up-regulated in all 6GA tissue specimens.2. The results from q RT-PCR showed that lnc RNA CTC was up-regulated in GA tissue samples, the up-regulated expression rate was 60.3(79/131), and the up-regulated fold change was 10.58. The expression of lnc RNACTC was significantly correlated with tumor size, TNM stage, vascular invasion, perineural invasion, and the GA tissue levels of RRM1 and Ki67, P < 0.05, and the difference was statistically significant.3. The preliminary cell experiment results showed that compared with the normal gastric mucosa epithelial cell GES-1, the expression of lnc RNA CTC was up-regulated in BGC-823, SGC-7901 and MGC-803 GA cells, P < 0.05. The expression of Lnc RNA CTC was significantly inhibited by transfecting si RNA against Lnc RNA CTC into GA cell lines BGC-823 and SGC-7901. Knockdown lnc RNA CTC decreased SGC-7901 and BGC-823 cell's proliferation(P < 0.001),inhibited SGC-7901's migration(P < 0.0001) and reduced SGC-7901 invasion(P< 0.0001). Compared with untreated control group, knockdown of lnc RNA CTC in SGC-7901 exhibited no significantly affecting on the apoptosis of GA cells.4. The q RT-PCR results obtained from analysis of parent chain gene AKT2 expression showed a certain correlation between lnc RNA CTC and AKT2 expression levels, and the correlation value of R =0.5873, P < 0.0001. The results revealed that the lnc RNA CTC expression levels were positively correlated with AKT2 m RNA expression levels, and had a certain interaction between lnc RNA CTC and AKT2. Both the expression levels of lnc RNAGK-IT1 and TRAF4-AS1 showed no statistical correlation with the expression levels of lnc RNA CTC.Conclusion:1. There are many lnc RNA showing aberrant levels of expression in GA tissues.One of the reasons of the occurrence of cancer may be related with the aberrant lnc RNAs expression. Lnc RNA CTC expression was up-regulated in all 6 GA tissues.2. Lnc RNA CTC may be involved in the development of GA. Tumor size, TNM stage, vascular invasion, perineural invasion, and GA tissue RRM1 and Ki67 levels were all correlated with lnc RNA CTC expression levels. Therefore,lnc RNA CTC can be used as a potential diagnostic marker for GA.3. Lnc RNA CTC was over-expressed in all BGC-823, SGC-7901, and MGC-803 GA cell lines. Knockdown of CTC expression by si RNA inhibited GA cell proliferation, migration and invasion, but did not significantly affect the apoptosis in GA cells.4. The expression levels of lnc RNA CTC and its parent chain gene AKT2 has a positive correlation, and the mechanism needs to be further investigated. The expression levels of lnc RNAGK-IT1, lnc RNATRAF4-AS1 and lnc RNA CTC exhibited no statistical correlation between each other. The independent expression of different Lnc RNAs may suggest that the expression of different Lnc RNA may have biological independence.5. In summary, the results of this investigation indicated that the aberrant expression of lnc RNA CTC was associated with GA. Detection the expression levels of lnc RNA CTC in GA tissues may predict disease progression and prognosis in patients with GA. Lnc RNA CTC could be used as one of molecular markers of GA. |
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