Let-7c-5p Down Regulates the Proliferation of Colorectal Cancer Through the MAPK-ERK-Signaling Pathway.
Juanjuan FuLongmei ZhouSijin LiWenjing HeJining ZhengZhiping HouPeiyuan HePublished in: Biochemical genetics (2023)
Colorectal cancer (CRC) is one of the most prevalent and life-threatening cancers. Rapid cell proliferation is the leading cause of cancer-related death in CRC. MicroRNAs (miRNAs) have been identified to play essential roles in the proliferation of CRC. Differential expression of let-7c-5p in CRC was assessed using a GEO dataset, and confirmed through RT-qPCR using CRC subject tissues. Let-7c-5p-overexpressing HCT8 cell line was constructed by transfecting let-7c-5p. Bioinformatics analysis identified that DUSP7 is the target gene of let-7c-5p. Further experimental assays, including Cell Counting Kit-8 (CCK8), EdU staining, cell colony, and Western Blot assays, confirmed the target genes and pathway of let-7c-5p. Receiver operator characteristic curve (ROC) analysis was performed to evaluate the diagnostic value of let-7c-5p for CRC. Finally, survival analysis was performed to determine the effect of DUSP7 and let-7c-5p on the prognosis of CRC patients. RT-qPCR analysis showed that the expression level of let-7c-5p was significantly increased in CRC subject tissues compared to the adjacent tissue. Overexpression of let-7c-5p promoted cell proliferation in HCT8 cell line. Furthermore, the MAPK-ERK pathway's protein expression of p-ERK1/2 was downregulated, while the ratio of Bcl-2/Bax was increased by let-7c-5p transfection in HCT 8. ROC analysis demonstrated that the expressive level of let-7c-5p had higher diagnostic value for CRC. Survival curve analysis indicated that high expression of DUSP7 and low expression of let-7c-5p were associated with poor prognosis in CRC patients. The findings suggest that let-7c-5p exerts an antitumor function by inhibiting the DUSP7-mediated MAPK-ERK pathway. Both DUSP7 and let-7c-5p have the potential to serve as prognostic biomarkers in CRC patients.
Keyphrases
- signaling pathway
- poor prognosis
- cell proliferation
- pi k akt
- end stage renal disease
- ejection fraction
- newly diagnosed
- chronic kidney disease
- long non coding rna
- induced apoptosis
- oxidative stress
- cell cycle arrest
- epithelial mesenchymal transition
- gene expression
- single cell
- stem cells
- south africa
- high throughput
- climate change
- dna methylation
- bone marrow
- transcription factor
- mesenchymal stem cells
- sensitive detection
- endoplasmic reticulum stress
- genome wide identification