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Karyopherin Subunit Alpha 1 Enhances the Malignant Behaviors of Colon Cancer Cells via Promoting Nuclear Factor-κB p65 Nuclear Translocation

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Abstract

Background/Aims

Aberrant nuclear factor-κB p65 (NF-κB p65) nuclear import commonly occurs in multiple cancers, including colon cancer. According to BioGRID, we noted that Karyopherin subunit alpha 1 (KPNA1), an important molecular transporter between the nucleus and the cytoplasm, may interact with NF-κB p65. KPNA1 itself is highly expressed in colon adenocarcinoma samples (N = 286) based on The Cancer Genome Atlas (TCGA) database. We aimed to explore the role of KPNA1 in colonic carcinogenesis and to determine whether NF-κB p65 nuclear translocation was involved.

Methods

KPNA1 expressions at mRNA and protein levels were analyzed in colon cancer tissues. The regulatory effect of KPNA1 on malignant biological properties was detected in SW480 and HCT116 colon cancer cells. Coimmunoprecipitation and immunofluorescence were performed to verify the relationship between KPNA1 and NF-κB p65. KPNA1 ubiquitination was also preliminarily investigated.

Results

KPNA1 was firstly confirmed as a significantly upregulated gene in our collected clinical colon cancer samples (N = 35). KPNA1 depletion inhibited cell proliferation, induced cell cycle arrest, and diminished migratory and invasive capacity of SW480 and HCT116 cells. Colon cancer cells overexpressing KPNA1 acquired more aggressive behaviors. KPNA1 acted as a transporter to induce the nuclear accumulation of NF-κB p65, thereby activating NF-κB signaling pathway in colon cancer cells. Furthermore, HECT, C2, and WW Domain-Containing E3 Ubiquitin (HECW2) interacted with KPNA1 to induce its ubiquitination. KPNA1 labeled with polyubiquitins was degraded through ubiquitin–proteasome system.

Conclusion

The present study uncovers a role of KPNA1-NF-κB p65 axis in promoting colonic carcinogenesis.

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Acknowledgments

Our work was supported by the experimental platform of Shengjing Hospital of China Medical University.

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Authors and Affiliations

  1. Department of Infectious Diseases, Shengjing Hospital of China Medical University, Shenyang, 110004, Liaoning, China

    Lianrong Zhao

  2. Department of General Surgery, Shengjing Hospital of China Medical University, No. 36, Sanhao Street, Heping District, Shenyang, 110004, Liaoning, China

    Di Wu, Qiao Qu, Zhilong Li & Hongzhuan Yin

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Correspondence to Hongzhuan Yin.

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10620_2023_7936_MOESM1_ESM.tif

Supplementary file1 Supplementary Fig. 1 HE straining was utilized to detect the presence of neoplastic cells in the clinical samples (at 40 X magnification). (TIF 2545 KB)

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Zhao, L., Wu, D., Qu, Q. et al. Karyopherin Subunit Alpha 1 Enhances the Malignant Behaviors of Colon Cancer Cells via Promoting Nuclear Factor-κB p65 Nuclear Translocation. Dig Dis Sci 68, 3018–3031 (2023). https://doi.org/10.1007/s10620-023-07936-y

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