Identifying the key genes and microRNAs in colorectal cancer liver metastasis by bioinformatics analysis and in�vitro experiments

Abstract

Colorectal cancer (CRC) is one of the principal causes of cancer-associated mortality worldwide. The high incidence of liver metastasis is the leading risk factor of mortality in patients with CRC, and the mechanisms of CRC liver metastasis are poorly understood. In the present study, 7 datasets, including 3 gene expression profile datasets and 4 microRNA (miRNA) expression profile datasets were downloaded from the NCBI Gene Expression Omnibus (GEO) database to identify potential key genes and miRNAs, which may be candidate biomarkers for CRC liver metastasis. Differentially expressed (DE) genes (DEGs) and DE miRNAs of primary CRC tumor tissues and liver metastatic CRC tumor tissues were selected using the GEO2R tool. Gene Ontology and Kyoto Encyclopedia of Gene and Genome pathway enrichment analyses were conducted using the Database for Annotation, Visualization and Integrated Discovery online database. Furthermore, Cytoscape with cytoHubba and the Molecular Complex Detection (MCODE) plug-in were used to visualize a protein-protein interaction (PPI) network for these DEGs, and to screen hub genes and gene modules in the PPI network. In addition, the online databases, TargetScan, miRanda, PITA, miRWalk and miRDB, were used to identify the target genes of the DE miRNAs. In the present study, 141 DEGs (97 upregulated and 44 downregulated) and 3 DE miRNAs (2 upregulated and 1 downregulated) were screened from the 3 gene expression microarray datasets and 4 miRNA expression microarray datasets, respectively. In total, 10 hub genes with a high degree of connectivity were selected from the PPI network, including albumin (ALB), coagulation factor II (F2), thrombin, apolipoprotein H (APOH), serpin family C member 1 (SERPINC1), apolipoprotein A1 (APOA1), α-1-microglobulin/bikunin precursor (AMBP), apolipoprotein C3 (APOC3), plasminogen (PLG), α-2 HS glycoprotein (AHSG) and apolipoprotein B (APOB). The most important module was detected in the PPI network using the MCODE plug-in. A total of 20 DEGs were identified to be potential target genes of these DE miRNAs, and novel miRNA-DEGs regulatory axes were constructed. In vitro experiments were performed to demonstrate that miR-885 promoted CRC cell migration by, at least partially, decreasing the expression of von Willebrand factor (vWF) and insulin-like growth factor binding protein 5 (IGFBP5). In conclusion, by using integrated bioinformatics analysis and in vitro experiments, key candidate genes were identified and novel miRNA-mRNA regulatory axes in CRC liver metastasis were constructed, which may improve understanding of the molecular mechanisms underlying CRC liver metastasis.

Systematic construction and validation of an immune prognostic model for lung adenocarcinoma

“…56 Single nucleotide polymorphisms (SNPs) in patients are usually related to moderate to serious bleeding phenotypes, while the G20210A mutation in the 3′ untranslated region of the F2 gene is a well-established risk factor for thrombophilia. 58 In the present study, F2 was overexpressed in LUAD and was associated with poor prognosis in patients with LUAD. 57 Patients with tumours have a higher risk of venous thromboembolism, and certain coagulation factors are related to the development of various types of cancers.…”

Renalase Attenuates Mouse Fatty Liver Ischemia/Reperfusion Injury through Mitigating Oxidative Stress and Mitochondrial Damage via Activating SIRT1

“…Si-STAT3 and matched si-NC were purposed from Ribo-Bio (Guangzhou, China) and transfected using Lipofectamine 3000 (Invitrogen, Thermo Fisher Scientific, Inc.) according to the manufacturer's protocols as previously described [21]. Briefly, HepG2 cells were in Opti-MEM (Gibco, Thermo Fisher Scientific, Inc.) with premixed Lipofectamine 3000 and si-STAT3 for 3 h. Then, the mixture was changed with DMEM medium with 10% FBS for 48 h. The sequences of siRNAs are shown in Supplementary Table 2. 2.6.…”

IGFBP5 increases cell invasion and inhibits cell proliferation by EMT and Akt signaling pathway in Glioblastoma multiforme cells

“…IGFBP5 is the most conserved of the IGFBPs and is frequently dysregulated in cancers and metastatic tissues [14]. Many studies have shown that IGFBP5 can suppress tumor proliferation and metastasis [15], while others have shown that IGFBP5 can function as an oncogene to promote tumor metastasis [16]. IGFBP5 has both IGF dependent and IGF independent regulatory effects on cell function.…”