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BACKGROUND: Colorectal cancer (CRC) is the fourth most prevalent cancer in the world. However, the molecular mechanism underlying CRC is largely unknown. OBJECTIVE: To explore the pathogenic mechanism of CRC and to facilitate better diagnosis and treatment of this disease. METHODS: Differentially expressed miRNAs (DEMs) and genes (DEGs) in CRC vs. Control samples from the miRNA expression data in GSE115513 and the miRNA and mRNA expression data in the TCGA-COAD dataset were screened, followed by the construction of the miRNAmRNA regulatory network. Functional and pathway enrichment analysis, protein-protein interaction (PPI) analysis, and survival analysis were then performed for these DEGs and DEMs. RESULTS: We identified 64 DEMs from the GSE115513 dataset and 265 DEMs and 2218 DEGs from the TCGA-COAD dataset. miR-27a-3p was a hub DEM with the highest degree in the miRNA-mRNA network, while GRIN2B and PCDH10 were hub DEGs targeted by multiple miRNAs, including miR-27a-3p. SNAP25 and GRIN2B were also hub DEGs with the highest degree of interactions in the PPI network. These DEMs and DEGs were significantly enriched in multiple KEGG pathways, including proteoglycans expression and cAMP signaling pathway in cancer. Finally, seven DEGs, including FJX1 Dsc2, and hsa-miR-375, were revealed to be correlated with CRC prognosis. CONCLUSION: Aberrant expressions of genes and miRNAs were involved in the pathogenesis of CRC, probably by regulating proteoglycans expression and cAMP signaling. miR-27a-3p, PCDH10, GRIN2B, FJX1, Dsc2, and hsa-miR-375 were identified as potential targets for understanding the pathogenic mechanism of CRC. In addition, FJX1, Dsc2 and hsa-miR-375 were identified as potential predictive markers for CRC prognosis.
Assuntos
Neoplasias Colorretais/genética , Redes Reguladoras de Genes , MicroRNAs/genética , RNA Mensageiro/genética , Biologia Computacional , HumanosRESUMO
[This corrects the article DOI: 10.18632/oncotarget.11888.].
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This study aimed to explore the effects of miR-21 and PTEN/Akt signaling pathway on TGF-ß1-induced epithelial-mesenchymal transition (EMT) in gastric cancer (GC). GC tissues and adjacent tissues were collected from 83 patients. The qRT-PCR assay was performed to detect miR-21 expression. The expressions of PTEN, Akt and p-Akt were detected by immunohistochemistry. After 48 h of treatment with TGF-ß1 (10 ng/mL), the SGC-7901 and KATO-III cells were divided into the blank, negative control (NC), miR-21 inhibitors, PTEN-siRNA and miR-21 inhibitors + PTEN-siRNA groups. EMT related factors and PTEN expressions were detected by qRT-PCR assay and Western blotting. The scratch test was conducted to observe cell migration. Xenograft tumor model in nude mice was used to evaluate the effects of miR-21 on EMT of GC cells in vivo. In GC tissues, the expressions of miR-21, Akt and p-Akt were up-regulated, while PTEN expression was down-regulated. Gene and protein expressions of E-cadherin and PTEN in the miR-21 inhibitors group were higher than the blank, NC, PTEN-siRNA and miR-21 inhibitors + PTEN-siRNA groups, while the expressions of N-cadherin, ß-catenin, Vimentin and Slug in the miR-21 inhibitors group were lower than other groups. MiR-21 inhibitors significantly inhibit cell migration and invasion in GC cell lines. In vivo xenograft experiment revealed that miR-21 inhibitor inhibits the growth of transplanted tumor through up-regulating E-cadherin and PTEN expressions and down-regulating the expressions of N-cadherin, ß-catenin, Vimentin and Slug. These results suggest that miR-21 could promote TGF-ß1-induced EMT in GC cells through up-regulating PTEN expression.