Effect of laminin subunit α3 on epithelial-mesenchymal transition， invasion， and metastasis abilities of pancreatic cancer

Nenghong YANG; Likun REN; She TIAN; Min HAN; Zhu LI; Yuxiang ZHAO; Peng LIU

doi:10.12449/JCH250219

Volume 41 Issue 2

Feb. 2025

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Article Navigation > Journal of Clinical Hepatology > 2025 > 41(2): 322-332

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Effect of laminin subunit α3 on epithelial-mesenchymal transition， invasion， and metastasis abilities of pancreatic cancer

DOI: 10.12449/JCH250219

1.
Department of Hepatobiliary Surgery，The Affiliated Hospital of Guizhou Medical University，Guiyang 550000，China
2.
Clinical School of Medicine，Guizhou Medical University，Guiyang 550000，China

Research funding:

Guizhou Provincial Science and Technology Program (QKH-JC2024-ZK［2024］230);

Guizhou Provincial Health Commission Science and Technology Fund Project (gzwkj2024-373)

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Corresponding author: LIU Peng， liupeng5061@126.com （ORCID： 0000-0003-0471-3836）
Received Date: 2024-06-05
Accepted Date: 2024-07-11
Published Date: 2025-02-25

Abstract

Abstract

Objective To investigate the effect of laminin subunit α3 （LAMA3） on the epithelial-mesenchymal transition （EMT）， invasion， and metastasis abilities of pancreatic cancer （PC）. Methods A comprehensive analysis was performed for tumor- and EMT-related databases to identify the EMT genes associated with PC， especially LAMA3. The methods of qRT-PCR and Western blot were used to measure the expression level of LAMA3 in PC tissue and cell lines； immunofluorescence assay was used to determine the localization of LAMA3 in PANC-1 cells； Transwell assay was used to investigate the effect of LAMA3 on the invasion and migration abilities of PC cells. The t-test was used for comparison of continuous data between groups. Results The analysis of the TCGA database identified 3 EMT-related oncogenes for PC， i.e.， LAMA3， AREG， and SDC1. The LASSO-Cox regression model showed that LAMA3 had the most significant impact on the prognosis of PC （risk score=0.256 1×LAMA3+0.043 1×SDC1+0.071 4×AREG）. The Cox model and nomogram showed that the high expression of LAMA3 was an independent risk factor for the poor prognosis of PC （hazard ratio=1.32， 95% confidence interval： 1.07‍ ‍—‍ 1.62， P<0.01）. Experimental results showed that there was a significant increase in the expression of LAMA3 in pancreatic cancer tissue compared with the normal pancreatic tissue. Compared with the HPDE cell line， there were varying degrees of increase in the expression of LAMA3 in pancreatic cancer AsPC-1， BxPC-3， PANC-1， MIA PaCa-2， and SW1990 cell lines， with the highest expression level in PANC-1 cells. The enrichment analysis showed that LAMA3 was associated with the biological processes and signaling pathways such as EMT， collagen metabolism， extracellular matrix degradation， the TGF-β pathway， and the PI3K pathway. After the knockdown of LAMA3， there were significant reductions in the expression levels of N-Cadherin， Vimentin， and Snail， while there was a significant increase in the expression level of E-Cadherin. Transwell assay showed that there were significant reductions in the invasion and migration abilities of PANC-1 cells after the knockdown of LAMA3. Conclusion LAMA3 is highly expressed in PC and can promote the EMT， invasion， and migration of PC cells， and therefore， LAMA3 may be used as a novel diagnostic marker and a new therapeutic target for PC.
- Pancreatic Neoplasms,
- Laminin,
- Epithelial-Mesenchymal Transition,
- Neoplasm Invasiveness,
- Neoplasm Metastasis

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References

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沈阳化工大学材料科学与工程学院沈阳 110142

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Effect of laminin subunit α3 on epithelial-mesenchymal transition， invasion， and metastasis abilities of pancreatic cancer

DOI: 10.12449/JCH250219

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Effect of laminin subunit α3 on epithelial-mesenchymal transition， invasion， and metastasis abilities of pancreatic cancer

DOI: 10.12449/JCH250219

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