关键词: 胃癌, 细胞增殖, 细胞侵袭, 微小RNA

Abstract: Objective To investigate the expression,function and molecular mechanism of lncRNA TONSL-AS1 in gastric cancer.Methods Collect cancer tissues and adjacent tissues(tissues which were 5 cm away from the lesion) from 71 patients with gastric cancer treated in our hospital.12 female nude mice weighing 18-22g were divided into NC group and mimic-TONSL group,with 6 mice in each group,and to prepare gastric cancer model.In gastric cancer cells,lncRNA TONSL-AS1 was overexpressed,and its effects on cell migration,proliferation,and invasion were assessed using Transwell experiments and a xenograft tumor model in nude mice.RNA pull down experiments coupled with protein mass spectrometry were employed to identify proteins interacting with lncRNA TONSL-AS1.By viral infection,the expression of lncRNA TONSL-AS1 binding protein was downregulated in gastric cancer cells.In vitro cell experiments and in vivo nude mouse tumorigenesis experiments were conducted to detect whether the binding protein affects the proliferation,migration,invasion,and in vivo tumorigenesis ability of gastric cancer cells.Candidate miRNAs(miRs) that potentially bind to lncRNA TONSL-AS1 were screened using bioinformatics analysis.By constructing cells with high expression of recombinant lentivirus miRNA and their control cells,and conducting in vivo and in vitro functional experiments,the ability of these cells to migrate and invade in vitro,as well as vivo tumorigenesis ability,was observed to evaluate the function of lncRNA TONSL-AS1 competitively binding miRNA.Results lncRNA TONSL-AS1 is lowly expressed in gastric cancer.High expression of lncRNA TONSL-AS1 can inhibit the proliferation of gastric cancer cells.YTH domain N6-methyladenine RNA binding protein 2(YTHDF2) has been identified as a binding protein of lncRNA TONSL-AS1.And YTHDF2 can promote the invasion and proliferation of gastric cancer cells by interacting with lncRNA TONSL-AS1.MiR-144 can regulate the expression of lncRNA TONSL-AS1 through competitive binding and inhibit the proliferation and invasion of gastric cancer cells.Conclusion lncRNA TONSL-AS1 can inhibit the proliferation of gastric cancer,while YTHDF2 can promote the invasion and proliferation of gastric cancer cells by interacting with lncRNA TONSL-AS1;miR-144 competitively binds to lncRNA TONSL-AS1 to inhibit the proliferation and invasion of gastric cancer cells.

Key words: gastric cancer, cell proliferation, cell invasion, microRNA