Abstract：
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.
摘要：
结直肠癌(CRC)是最常见和危及生命的癌症之一。快速细胞增殖是CRC中癌症相关死亡的主要原因。MicroRNAs(miRNA)已被鉴定为在CRC的增殖中起重要作用。使用GEO数据集评估CRC中let-7c-5p的差异表达，并使用CRC受试者组织通过RT-qPCR确认。通过转染let-7c-5p构建过表达let-7c-5p的HCT8细胞系。生物信息学分析确定DUSP7是let-7c-5p的靶基因。进一步的实验测定，包括细胞计数套件-8（CCK8），EdU染色,细胞集落,和蛋白质印迹分析，证实了let-7c-5p的靶基因和通路。采用受试者工作特征曲线(ROC)分析评价let-7c-5p对CRC的诊断价值。最后,进行生存分析以确定DUSP7和let-7c-5p对CRC患者预后的影响.RT-qPCR分析显示,与邻近组织相比,let-7c-5p的表达水平在CRC受试者组织中显著增加。过表达let-7c-5p促进HCT8细胞增殖。此外，MAPK-ERK通路的p-ERK1/2蛋白表达下调，而在HCT8中，通过let-7c-5p转染增加了Bcl-2/Bax的比率。ROC分析显示let-7c-5p的表达水平对CRC有较高的诊断价值。生存曲线分析表明DUSP7高表达和let-7c-5p低表达与CRC患者预后不良相关。研究结果表明，let-7c-5p通过抑制DUSP7介导的MAPK-ERK途径发挥抗肿瘤功能。DUSP7和let-7c-5p都有可能作为CRC患者的预后生物标志物。
