| Gastric cancer is one of the most common malignant tumors of gastric mucosa epithelial cells. The morbidity and mortality of gastric cancer is the highest in the world in developing countries especially in China. Despite surgery is considered to be the main method of diagnosis and treatment of gastric cancer,5-year survival rate of the patients is still less than 20%. Besides the traditional treatment measures, to explore the molecular mechanisms of gastric cancer is of great importance to develop effective targeted drugs. A growing number of studies have found that many molecular regulators play an important role in the development of gastric cancer, such as miRNAs, oncogene, RNA binding proteins. The abnormal expression of these genes are likely to cause changed cell biological behavior, leading to the tumorigenesis. The function of these genes and their related gene expression regulation in carcinogenesis have become the focus of cancer research.miRNAs is the 20?25 nucleotides single-stranded RNA, which is generated from the 70?90 bases single-stranded RNA precursors with hairpin structure processed by dicer enzyme, but the miRNAs itself is not translated into proteins. miRNAs mainly involved in post-transcriptional gene regulation in prokaryotic and eukaryotic, which regulates a variety of cell biological processes. The differential expression of miRNAs in many kinds of cancers suggests that miRNAs act as oncogenes or tumor suppressor in tumorigenesis.Oncogene can be activated from proto-oncogene by mutation, translocation and so on. The abnormal expression of the encoded protein, will lead to carcinogenesis. The inactivation and silence of tumor suppressors are also associated with tumor development. Mutations, deletion or translocation can cause aberrant expression of tumor suppressors and finally lead to tumorigenesis. Therefore, the further research of oncogenes and tumor suppressor mediated molecular pathway will contribute to find the new ways and methods of diagnosis and treatment of the tumor.There is also a class of RNA binding proteins in cells. It has high affinity with mRNA via cis regulatory elements and leads to mRNA deadenylation and degradation directly or indirectly. Accumulating evidence suggests that RBPs play important roles in cell division, differentiation, proliferation, cell cycle and apoptosis. In normal cells, RBPs-mediated pathways can repair gene abnormality due to the chromosome replication process. However, the aberrant expression of RBPs can cause instability of oncogene and its related inflammatory factor, and eventually tumorigenesis. It is of great impotance to clarify the above factors mediated molecular mechanism in gastric cancer development and develop effective therapeutic target. In this paper, the main content is as follows:1. To investigate the effects of miR-760 on cell proliferation, migration and invasion of gastric cancer cell line MGC-803.The level of miR-760 expression was detected by real-time PCR in 50 paired gastric cancer tissues and their adjacent normal tissues. miR-760 overexpression was achieved by transfection of construct pcDNA-miR-760 into MGC-803 cells. The proliferation, migration and invasion of MGC-803 cells were detected by the CCK-8, Transwell and scratch wound assay, respectively. The results show that miR-760 was decreased in 36 cases (72%) of gastric cancer tissues compared to their control. Furthermore, overexpression of miR-760 effectively inhibited the migration and invasion of MGC-803 cells (P< 0.05), but had no effects on proliferation. The results infered that down-regulation of miR-760 has a correlation with the progression of gastric cancer. Re-introduction of miR-760 can inhibit the invasion and migration of MGC-803 cells.2. To investigate the effects of Eaf2 on cell proliferation, migration and invasion of gastric cancer cell line MGC-803The level of Eaf2 expression was detected by real-time PCR in 50 paired gastric cancer tissues and their adjacent normal tissues. Eaf2 overexpression was achieved by transfection of construct pcDNA-Eaf2 into MGC-803 cells. The proliferation, migration and invasion of MGC-803 cells were detected by the CCK-8, Transwell and scratch wound assay, respectively. Eaf2 was decreased in 42 cases (84%) of gastric cancer tissues compared to their control in this results. Furthermore, overexpression of Eaf2 effectively inhibited the migration, invasion and proliferation of MGC-803 cells (p< 0.05). To sum up, down-regulation of Eaf2 has a correlation with the progression of gastric cancer.3. Alternative pre-mRNA splicing by RBPs is a key mechanism in gastric cancer developmentEmerging evidence indicates that splicing program is frequently deregulated during tumorigenesis, and cancer cells favor to produce protein isoforms that can promote growth and survival. RNA binding protein QKI-5 is a critical regulator of alternative splicing in an expanding list of primary human tumors and tumor cell lines, however its biological role and regulatory mechanism in gastric cancer development and progression are poorly defined. In this study, we demonstrated that the down-regulation of QKI-5 was associated with pTNM stage and pM state of gastric cancer patients. Re-introduction of QKI-5 inhibited gastric cancer cell proliferation, migration and invasion in vitro and in vivo, which might be due to the altered splicing pattern of macroH2Al pre-mRNA, leading to the accumulation of macroH2A1.1 isform. Furthermore, QKI-5 could inhibit CCNL1 expression via promoting macroH2A1.1 production. Thus, these results identify a novel regulatory axis involved in gastric tumorigenesis and provide a new strategy for gastric cancer therapy. |
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