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.
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All data are available from the corresponding author on request.
Change history
21 February 2024
A Correction to this paper has been published: https://doi.org/10.1007/s10528-024-10736-2
References
Ashburner M, Ball CA, Blake JA et al (2000) Gene ontology: tool for the unification of biology. The Gene Ontology Consortium. Nat Genet 25(1):25–29
Bai H, Song M, Jiao R et al (2021) DUSP7 inhibits cervical cancer progression by inactivating the RAS pathway. J Cell Mol Med 25(19):9306–9318
Bech JM et al (2023) Proteomic profiling of colorectal adenomas identifies a predictive risk signature for development of metachronous advanced colorectal neoplasia. Gastroenterology 165(1):121–132
Chen H, Tong T, Lu SY et al (2023) Urea cycle activation triggered by host-microbiota maladaptation driving colorectal tumorigenesis. Cell Metab 35(4):651–666
Corrà F et al (2018) The Network of non-coding RNAs in cancer drug resistance. Front Oncol 8:327
Du M et al (2023) Integrated multi-omics approach to distinct molecular characterization and classification of early-onset colorectal cancer. Cell Rep Med 4(3):100974
Gene Ontology Consortium (2021) The Gene Ontology resource: enriching a GOld mine. Nucleic Acids Res 49(D1):D325–D334
Harrandah AM, Mora RA, Chan EKL (2018) Emerging microRNAs in cancer diagnosis, progression, and immune surveillance. Cancer Lett 438:126–132
Hill M, Tran N (2021) miRNA interplay: mechanisms and consequences in cancer. Dis Model Mech 14(4):dmm047662
Kanehisa M, Goto S (2000) KEGG: kyoto encyclopedia of genes and genomes. Nucleic Acids Res 28(1):27–30
Kanehisa M, Furumichi M, Sato Y et al (2023) KEGG for taxonomy-based analysis of pathways and genomes. Nucleic Acids Res 51(D1):D587–D592
Latest global cancer data: cancer burden rises to 19.3 million new cases and 10.0 million cancer deaths in 2020 questions and answers (Q&A) (2020) https://gco.iarc.fr/
Wang C, Xue H, Zhao R et al (2022) RGS16 regulated by let-7c-5p promotes glioma progression by activating PI3K-AKT pathway. Front Med
Winawer SJ, Zauber AG, Ho MN et al (1993) Prevention of colorectal cancer by colonoscopic polypectomy. The National Polyp Study Workgroup. N Engl J Med 329(27):1977–1981
Wu Y, Zhang Y, Zheng X et al (2020) Circular RNA circCORO1C promotes laryngeal squamous cell carcinoma progression by modulating the let-7c-5p/PBX3 axis. Mol Cancer 19(1):1–18
Zheng Y, Luo M, Lü M et al (2020) Let-7c-5p inhibits cell proliferation and migration and promotes apoptosis via the CTHRC1/AKT/ERK pathway in esophageal squamous cell carcinoma. Onco Targets Ther 13:11193–11209
Acknowledgements
The authors thank the financial support of Hebei Provincial of Human Resources and Social Security as well as Chengde Medical University.
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The study was supported by Hebei Provincial of Human Resources and Social Security (CY201701, CY201702).
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FJJ, HZP and HPY designed the study and wrote the manuscript. LSJ and ZLM carried out data analysis, HWJ prepared pathological slides. All authors have read and approved the manuscript.
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Fu, J., Zhou, L., Li, S. et al. Let-7c-5p Down Regulates the Proliferation of Colorectal Cancer Through the MAPK-ERK-Signaling Pathway. Biochem Genet (2023). https://doi.org/10.1007/s10528-023-10581-9
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DOI: https://doi.org/10.1007/s10528-023-10581-9