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miR-1180 Targets FXYD5 to Regulate Pancreatic Cancer Cells Migration and Invasion

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Abstract

Pancreatic cancer is a fatal malignancy typically diagnosed in older males and has an aggressive progression. The function of the miR-1180/FXYD5 axis in pancreatic cancer malignant behaviors was investigated. 20 pairs of pancreatic cancer and adjacent normal tissue samples were harvested from pancreatic cancer patients, and qRT-PCR, IHC, and western blot assays were performed, respectively, to detect the mRNA expression and protein levels of miR-1180 or FXYD5. Transwell and scratch assays were conducted to detect the migratory and invasive ability of pancreatic cancer cells; a Dual-luciferase reporter assay was employed to validate miR-1180 targeting FXYD5. miR-1180 targeting FXYD5 to regulate the migratory and invasive ability of pancreatic cancer cells was validated in mouse xenograft tumor models. FXYD5 expression was increased in pancreatic cancer tissue samples than in adjacent normal tissue samples (P < 0.01), and FXYD5 expression exhibited a positive correlation with the migratory and invasive ability of pancreatic cancer cells. miR-1180 targeted FXYD5 and negatively regulated FXYD5. Restoring miR-1180 expression could inhibit the migratory and invasive ability of pancreatic cancer cells (P < 0.01), and this effect could potentially be alleviated by FXYD5 overexpression. The miR-1180/FXYD5 axis positively regulated E-cadherin and negatively regulated MMP2 and MMP9 expression levels. In vivo findings demonstrated that miR-1180 overexpression inhibited tumor growth and lung metastasis (P < 0.05), while FXYD5 overexpression promoted tumor growth and lung metastasis (P < 0.05). In conclusion, the miR-1180 /FXYD5 axis could be involved in pancreatic cancer metastasis through the regulation of EMT and extracellular matrix degradation.

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The authors confirm that the data supporting the findings of this study are available within the article.

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Acknowledgments

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Funding

This study was supported by the Fund of Zhongshan Science and Technology Bureau (2021B1139).

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Authors and Affiliations

  1. Department of Gastroenterology, Zhujiang Hospital of Southern Medical University, No. 253 Industrial Road, Guangzhou, 510280, Guangdong, China

    Hongmin Xie, Min Lu & Hua Mao

  2. Department of Gastroenterology, Zhongshan Chenxinghai Hospital of Integrated Traditional Chinese and Western Medicine, Zhongshan, 528415, Guangdong, China

    Hongmin Xie, Jiaxuan Li & Ruijiang Zhang

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  1. Hongmin Xie
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  2. Jiaxuan Li
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  3. Min Lu
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  4. Ruijiang Zhang
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Contributions

HX and HM contributed to the experimental design and supervised the whole experimental process; JL was involved in the experimental conducting; ML and RZ contributed to the data analysis and manuscript preparation. All the authors read, revised, and approved the final manuscript.

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Correspondence to Hua Mao.

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Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of Zhongshan Chenxinghai Hospital of Integrated Traditional Chinese and Western Medicine (approval No. 2021049) and with the 1964 Helsinki Declaration. Informed consent to participate in the study has been obtained from participants. The guidelines for the care and use of animals were approved by the Medicine Animal Welfare Committee of Zhongshan Chenxinghai Hospital of Integrated Traditional Chinese and Western Medicine (approval No. 2021049).

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Xie, H., Li, J., Lu, M. et al. miR-1180 Targets FXYD5 to Regulate Pancreatic Cancer Cells Migration and Invasion. Mol Biotechnol (2023). https://doi.org/10.1007/s12033-023-00923-8

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  • DOI: https://doi.org/10.1007/s12033-023-00923-8

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