Department of Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, China.
Genet Res (Camb). 2022 Oct 21;2022:2907554. doi: 10.1155/2022/2907554. eCollection 2022.
Colon cancer is the most common malignant tumor of the gastrointestinal tract, and approximately 80%-90% of colon cancers are colon adenocarcinomas (COADs). This study aimed to screen key microRNAs (miRNAs) associated with COAD. Differentially expressed (DE) miRNAs were screened between COAD and adjacent cancer samples based on the Gene Expression Omnibus (GEO) and the Cancer Genome Atlas obtained from datasets. The miRNAs of interest were validated using quantitative real-time polymerase chain reaction. Moreover, the effects of hsa-miR-135b-5p on the biological behavior of COAD cells were observed. To obtain the target genes of hsa-miR-135b-5p, transcriptome sequencing of the SW480 cells was performed, followed by protein-protein interaction (PPI) network and hsa-miR-135b-5p-target gene regulatory network construction and prognostic analysis. Downregulation of hsa-miR-135b-5p significantly inhibited SW480 cell proliferation, migration, and invasion and significantly facilitated apoptosis ( < 0.05). A total of 3384 DEmRNAs were screened, and enrichment analysis showed that the upregulated mRNAs were enriched in 25 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and 326 Gene Ontology Biological Processes (GO-BPs) while the downregulated mRNAs were enriched in 20 KEGG pathways and 276 GO-BPs. A PPI network was then constructed, and H2BC14, H2BC3, and H4C11 had a higher degree. In addition, a total of 352 hsa-miR-135b-5p-gene regulatory relationships were identified. Prognostic analysis showed that , , , , , and had prognostic significance ( < 0.05). In addition, the validation analysis results showed that , , and were significantly expressed between the miR-135b-5p-inhibitor and negative control groups ( < 0.05). Therefore, downregulation of hsa-miR-135b-5p inhibits cell proliferation, migration, and invasion in COAD, and carcinogenesis may function by targeting , , , , , and .
结肠癌是最常见的胃肠道恶性肿瘤，约 80%-90%的结肠癌为结肠腺癌（COAD）。本研究旨在筛选与 COAD 相关的关键微小 RNA（miRNA）。基于基因表达综合数据库（GEO）和癌症基因组图谱（TCGA），从数据集筛选 COAD 与癌旁组织差异表达的 miRNAs。采用实时定量聚合酶链反应（qRT-PCR）验证感兴趣的 miRNAs。此外，观察了 hsa-miR-135b-5p 对 COAD 细胞生物学行为的影响。为获得 hsa-miR-135b-5p 的靶基因，对 SW480 细胞进行转录组测序，构建蛋白-蛋白互作（PPI）网络和 hsa-miR-135b-5p-靶基因调控网络，并进行预后分析。下调 hsa-miR-135b-5p 显著抑制 SW480 细胞的增殖、迁移和侵袭，促进细胞凋亡（ < 0.05）。筛选出 3384 个差异表达信使 RNA（DEmRNA），富集分析显示，上调的 mRNAs 富集于 25 个京都基因与基因组百科全书（KEGG）通路和 326 个基因本体论生物过程（GO-BP），而下调的 mRNAs 富集于 20 个 KEGG 通路和 276 个 GO-BP。构建 PPI 网络，H2BC14、H2BC3 和 H4C11 具有较高的度。此外，共鉴定出 352 个 hsa-miR-135b-5p-基因调控关系。预后分析显示，、、、、和具有预后意义（ < 0.05）。此外，验证分析结果显示，miR-135b-5p 抑制剂组与阴性对照组之间的、、和表达水平差异有统计学意义（ < 0.05）。因此，下调 hsa-miR-135b-5p 抑制 COAD 细胞的增殖、迁移和侵袭，其致癌作用可能通过靶向、、、、和发挥作用。
