Yang Ming, Lu Zhixing, Yu Bowen, Zhao Jiajia, Li Liang, Zhu Kaiyu, Ma Min, Long Fei, Wu Runliu, Hu Gui, Huang Lihua, Chou Jing, Gong Ni, Yang Kaiyan, Li Xiaorong, Zhang Yi, Lin Changwei
Department of Gastrointestinal Surgery, The Third Xiangya Hospital of Central South University, Changsha 410013, China.
The Five-Year Program in Clinical Medicine, Xiangya School of Medicine, Central South University, Changsha 410013, China.
Cancers (Basel). 2022 Jul 1;14(13):3244. doi: 10.3390/cancers14133244.
MicroRNAs (miRNAs) and their target genes have been shown to play an important role in gastric cancer but have not been fully clarified. Therefore, our goal was to identify the key miRNA-mRNA regulatory network in gastric cancer by utilizing a variety of bioinformatics analyses and experiments. A total of 242 miRNAs and 1080 genes were screened from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), respectively. Then, survival-related differentially expressed miRNAs and their differentially expressed target genes were screened. Twenty hub genes were identified from their protein-protein interaction network. After weighted gene co-expression network analysis was conducted, we selected miR-137-3p and its target gene, COL5A1, for further research. We found that miR-137-3p was significantly downregulated and that overexpression of miR-137-3p suppressed the proliferation, invasion, and migration of gastric cancer cells. Furthermore, we found that its target gene, COL5A1, could regulate the expression of another hub gene, FSTL1, by sponging miR-137-3p, which was confirmed by dual-luciferase reporter assays. Knockdown of COL5A1 inhibited the proliferation, invasion, and migration of gastric cancer cells, which could be rescued by the miR-137-3p inhibitor or overexpression of FSTL1. Ultimately, bioinformatics analyses showed that the expression of FSTL1 was highly correlated with immune infiltration.
微小RNA(miRNA)及其靶基因已被证明在胃癌中发挥重要作用,但尚未完全阐明。因此,我们的目标是通过各种生物信息学分析和实验,确定胃癌中的关键miRNA-信使核糖核酸(mRNA)调控网络。分别从癌症基因组图谱(TCGA)和基因表达综合数据库(GEO)中筛选出总共242个miRNA和1080个基因。然后,筛选出与生存相关的差异表达miRNA及其差异表达的靶基因。从它们的蛋白质-蛋白质相互作用网络中鉴定出20个枢纽基因。进行加权基因共表达网络分析后,我们选择了miR-137-3p及其靶基因COL5A1进行进一步研究。我们发现miR-137-3p显著下调,并且miR-137-3p的过表达抑制了胃癌细胞的增殖、侵袭和迁移。此外,我们发现其靶基因COL5A1可以通过结合miR-137-3p来调节另一个枢纽基因FSTL1的表达,这通过双荧光素酶报告基因实验得到证实。COL5A1的敲低抑制了胃癌细胞的增殖、侵袭和迁移,而miR-137-3p抑制剂或FSTL1的过表达可以挽救这种抑制作用。最终,生物信息学分析表明FSTL1的表达与免疫浸润高度相关。