Open Access

CHL1 inhibits cell proliferation, migration and invasion by regulating the NF‑κB signaling pathway in colorectal cancer

  • Authors:
    • Ming Bao
    • Shenglong Li
    • Yu Zhu
    • Xiaoyu Dong
    • Ran Wang
    • Fangyan Jing
  • View Affiliations

  • Published online on: February 26, 2024     https://doi.org/10.3892/etm.2024.12454
  • Article Number: 165
  • Copyright: © Bao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Cell adhesion molecule close homolog of L1 (CHL1) is implicated in tumorigenesis of various malignancies. However, its role and underlying molecular mechanisms in colorectal cancer (CRC) remain unclear. The present study aimed to evaluate the specific biological functions and mechanisms of CHL1, in order to provide a theoretical basis for the use of CHL1 as a biological target in CRC. CHL1 expression was originally determined in CRC cell lines. Subsequently, CHL1 overexpression was induced by plasmid transfection in HT29 and SW480 cells, and cell proliferation, migration and invasion were evaluated using the Cell Counting Kit‑8, clone formation, organoids formation and Transwell assays. Immunofluorescence and western blotting were performed to assess the protein expression of E‑cadherin or N‑cadherin. Differentially expressed genes (DEGs) were further evaluated using RNA‑sequencing (RNA‑seq) in HT29 and SW480 cells following CHL1 overexpression and functional enrichment analysis. Western blotting was performed to validate the expression of proteins related to the nuclear factor κB (NF‑κB) signaling pathway. The TNMplot online database revealed the significant downregulation of CHL1 in CRC tissues. The results indicated that exogenous CHL1 overexpression significantly inhibited the proliferative, organoid‑forming, migratory and invasive abilities of HT29 and SW480 cells, and increased E‑cadherin protein expression. Additionally, CHL1 overexpression reduced xenograft tumor growth in vivo. RNA‑seq and functional analysis revealed that DEGs in CHL1 overexpressing cells were mainly enriched in the NF‑κB signaling pathway. The expression of p‑p65 and p‑p65/p65 ratio were significantly reduced in HT29 and SW480 cells, following CHL1 overexpression. Additionally, the inhibitory effects of CHL1 overexpression on CRC cell proliferation, organoid formation, migration and invasion were partially counteracted following the overexpression of p65 expression. Overall, the present study demonstrates that CHL1 inhibits CRC cell growth, migration and invasion through the inactivation of the NF‑κB signaling pathway.
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April-2024
Volume 27 Issue 4

Print ISSN: 1792-0981
Online ISSN:1792-1015

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Copy and paste a formatted citation
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Spandidos Publications style
Bao M, Li S, Zhu Y, Dong X, Wang R and Jing F: CHL1 inhibits cell proliferation, migration and invasion by regulating the NF‑κB signaling pathway in colorectal cancer. Exp Ther Med 27: 165, 2024
APA
Bao, M., Li, S., Zhu, Y., Dong, X., Wang, R., & Jing, F. (2024). CHL1 inhibits cell proliferation, migration and invasion by regulating the NF‑κB signaling pathway in colorectal cancer. Experimental and Therapeutic Medicine, 27, 165. https://doi.org/10.3892/etm.2024.12454
MLA
Bao, M., Li, S., Zhu, Y., Dong, X., Wang, R., Jing, F."CHL1 inhibits cell proliferation, migration and invasion by regulating the NF‑κB signaling pathway in colorectal cancer". Experimental and Therapeutic Medicine 27.4 (2024): 165.
Chicago
Bao, M., Li, S., Zhu, Y., Dong, X., Wang, R., Jing, F."CHL1 inhibits cell proliferation, migration and invasion by regulating the NF‑κB signaling pathway in colorectal cancer". Experimental and Therapeutic Medicine 27, no. 4 (2024): 165. https://doi.org/10.3892/etm.2024.12454