miR-1229-3p inhibits the malignant progression of colorectal cancer and serves as a potential biomarker

Abstract

Objective: To investigate the role and clinical application of microRNA in the malignant progression of colorectal cancer (CRC). Methods: The transcriptome data of human colorectal cancer and adjacent tissues from TCGA database were analyzed to screen out the differentially expressed microRNAs (miRNAs), among which miR-1229-3p with the most significant difference was selected as the target miRNA, and furthermore the expression of miR-1229-3p was verified through GEO and Starbase databases. The biological functional characteristics of miR-1229-3p was analyzed through Bioinformatics. The miR-1229-3p overexpression cell line and miR-1229-3p knockdown cell line were constructed. The effect of miR-1229-3p on the proliferation, metastasis, and apoptosis of CRC cells was explored in vitro by CCK-8 experiment, cloning formation experiment, EdU experiment, transwell, and flow cytometry experiment. The effect of miR-1229-3p on the prolife-rative capacity of CRC in vivo was explored by nude mouse transplantation tumor experiment. The target genes of miR-1229-3p were screened out by DIANA, TargetScan, and miRDB databases. KEGG and GO were used to analyze the biological function of target genes. The expression of miR-1229-3p in plasma exosomes of 60 CRC patients and 60 healthy examiners obtained from Nanjing First Hospital were analyzed, and receiver operating characteristic curve (ROC) was used to distinguish its diagnostic efficacy for CRC patients. Results: The expression of miR-1229-3p was downregulated in CRC cells and tissues. Bioinformatics predicted a significant negative correlation between miR-1229-3p and tumor progression pathways, such as epithelial-mesenchymal transition and angiogenesis (R<0, P<0.05). In vitro and in vivo studies showed that after the overexpression of miR-1229-3p, the proliferation, migration and invasion of CRC cells were inhibited, and the potential target gene SETD7 was downregulated, while the apoptosis of CRC cells could be inhibited after downregulating miR-1229-3p. miR-1229-3p from plasma exosomes of CRC was downregulated, which could distinguish CRC patients from normal people. ROC curve showed that the optimal critical value of miR-1229-3p for diagnosing CRC was 0.586 8, and the area under the curve was 0.863 2 (P<0.01). Conclusions: The expression of miR-1229-3p is downregulated in CRC, and SETD7 is a potential target gene for miR-1229-3p. miR-1229-3p can inhibit the proliferation, migration and invasion of CRC cells, and promote apoptosis of CRC cells. miR-1229-3p can be served as a potential biomarker for CRC diagnosis.

Keywords

• |colorectal cancer|mir-1229-3p|setd7|exosomes|biomarker