miR-647 and miR-1914 promote cancer progression equivalently by downregulating nuclear factor IX in colorectal cancer

摘要

MicroRNAs (miRNAs/miRs) have been investigated as diagnostic and prognostic biomarkers for cancer; however, the significance of miRNAs in colorectal cancer (CRC) remains to be elucidated. The aim of the present study was to determine the genetic profiles of CRC tissue, and screen for miRNAs implicated in CRC cell proliferation and migration. RNA sequencing of 10 paired specimens was performed to for screen genes that were upregulated or downregulated in CRC. miRNA expression in CRC specimens and cell lines was confirmed using qPCR analysis. The significance of indicated miRNAs in CRC cell proliferation and migration was evaluated using MTT and scratch wound-healing assays. Online computational prediction, isobaric tags for relative and absolute quantification analysis and a luciferase reporter assay were applied to determine candidate targeted genes for the miRNAs. RNA-seq data revealed miR-1914 as the most prominent miRNA in CRC specimens. qPCR analysis also suggested that the expression of miR-1914, as well as its counterpart miR-647 were elevated in CRC specimens and cell lines. Suppression of miR-647/1914 using small interfering RNAs inhibited CRC SW480 and SW620 cell proliferation, and migration. Nuclear factor I/X (NFIX) was demonstrated to be a candidate for miR-647/1914 and mediated the oncogenic activity of miR-647/1914. In all, miR-647 and miR-1914 were demonstrated to promote the proliferation and migration of CRC cells by directly targeting NFIX. Therapeutic delivery of siRNAs targeting miR-647/1914 and overexpression of NFIX may be feasible approaches for CRC treatment.