MicroRNA-485-5p targets keratin17 to regulate pancreatic cancer cell proliferation and invasion via the FAK / SRC / ERK pathway

Chen, Peng; Pan, Meng; Shen, Zhengchao; Yang, Yuquan; Wang, Xiaoming

doi:10.7150/jca.90689

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J Cancer 2024; 15(7):2033-2044. doi:10.7150/jca.90689 This issue Cite

Research Paper

MicroRNA-485-5p targets keratin17 to regulate pancreatic cancer cell proliferation and invasion via the FAK / SRC / ERK pathway

Peng Chen^1,*, Meng Pan^1,*, Zhengchao Shen², Yuquan Yang¹, Xiaoming Wang^2,✉

1. Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Wannan Medical College, Wuhu, Anhui 241000, P.R. China.
2. Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wannan Medical College, Wuhu, Anhui 241001, P.R. China.
*Peng Chen and Meng Pan are co-first authors

Citation:

Chen P, Pan M, Shen Z, Yang Y, Wang X. MicroRNA-485-5p targets keratin17 to regulate pancreatic cancer cell proliferation and invasion via the FAK / SRC / ERK pathway. J Cancer 2024; 15(7):2033-2044. doi:10.7150/jca.90689. https://www.jcancer.org/v15p2033.htm

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Abstract

Background: It is crucial to probe into the biological effect and mechanism of miRNA-485-5p regulating keratin 17 (KRT17) in pancreatic cancer (PC) to understand its pathogenesis and identify potential biological targets.

Methods: The bioinformatics means were used to evaluate the clinical significance of KRT17 expression in the Cancer Genome Atlas (TCGA) database. TargetScan database analysis in conjunction with dual luciferase and RNA Immunoprecipitation (RIP) experiments was used to probe the interaction relationship of miRNA-485-5p with KRT17. The expression of miRNA-485-5p and KRT17 in PC tissue and cancer cell lines was detected by Q-PCR paired with western blot assay. The biological function of miRNA-485-5p in regulating KRT17 was investigated in the PC cell line via gene silencing/overexpression technique. A western blot experiment was utilized to investigate the regulatory effect of KRT17 on cell cycle-related proteins and the FAK/Src/ERK signal pathway.

Results: The level of KRT17 was increased in PC tissues and this significantly decreased the survival rate of PC patients. TargetScan in combination with dual luciferase and RIP experiments verified the miRNA-485-5p target KRT17. The expression of KRT17 was high in the PC cell line, although the expression of miRNA-485-5p was low. Silencing KRT17 or overexpression of miRNA-485-5p significantly inhibited PC cell viability, proliferation, invasion, and colony formation, while promoting apoptosis. Overexpression of KRT17 drastically reversed the function of miRNA-485-5p. The silenced KRT17 remarkably downregulated the expression of cyclinD1, Cyclin Dependent Kinase 1 (CDK1), CDK2, Phospho-Focal Adhesion Kinase (p-FAK), p-Src, and p-ERK proteins in the PC cells.

Conclusion: Generally, an essential signaling cascade of miRNA-485-5p/KRT17/FAK/Src/ERK influences the biological functions of PC cells.

Keywords: Pancreatic cancer, KRT17, MiRNA-485-5p, Cell cycle, Proliferation

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APA

Chen, P., Pan, M., Shen, Z., Yang, Y., Wang, X. (2024). MicroRNA-485-5p targets keratin17 to regulate pancreatic cancer cell proliferation and invasion via the FAK / SRC / ERK pathway. Journal of Cancer, 15(7), 2033-2044. https://doi.org/10.7150/jca.90689.

ACS

Chen, P.; Pan, M.; Shen, Z.; Yang, Y.; Wang, X. MicroRNA-485-5p targets keratin17 to regulate pancreatic cancer cell proliferation and invasion via the FAK / SRC / ERK pathway. J. Cancer 2024, 15 (7), 2033-2044. DOI: 10.7150/jca.90689.

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CSE

Chen P, Pan M, Shen Z, Yang Y, Wang X. 2024. MicroRNA-485-5p targets keratin17 to regulate pancreatic cancer cell proliferation and invasion via the FAK / SRC / ERK pathway. J Cancer. 15(7):2033-2044.

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