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Trim44 facilitates the migration and invasion of human lung cancer cells via the NF-κB signaling pathway

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Abstract

Background

Trim44 is an important member of the tripartite motif-containing protein (TRIM) family. Recent research reported that Trim44 might play an important role in tumorigenesis, although its role in non-small cell lung cancer (NSCLC) and the related mechanisms is not yet known.

Methods

In this study we analyzed 30 pairs of NSCLC tumors and the matched adjacent normal tissue to define the relationship between Trim44 and NSCLC tumors. The function of Trim44 in cell migration and invasion was determined by overexpression of Trim44 in normal bronchial epithelial cell line 16HE or knockdown of Trim44 in A549 cells, respectively. Whether Trim44-mediated NF-κB signaling activation was involved in Trim44-mediated promotion of lung cancer was tested by q-PCR analysis and cell migration and invasion assay using PDTC, an inhibitor of NF-κB.

Results

We found that Trim44 was upregulated in NSCLC tumors (14/30 cases; 46.7 %). Furthermore, Trim44 was upregulated in many NSCLC cell lines, especially in A549 and H441. Moreover, Trim44 significantly enhanced cell migration and invasion ability, which was related to increased CXCR6 and matrix metalloproteinase 9 (MMP9). Knockdown of Trim44 in A549 cells by siRNA showed a diminished effect in cell migration and invasion. Further investigation revealed that blocking the NF-κB signaling pathway using PDTC, an inhibitor of NF-κB, reversed the expression of CXCR6 and MMP9, and alleviated the promotion of migration and invasion mediated by Trim44.

Conclusions

Our data suggest that Trim44 promotes NSCLC development through activation of NF-κB signaling via upregulating CXCL16 and MMP9 expression.

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Acknowledgments

This work was supported by grants from the Shanghai Chest Hospital Science and Technology Fund Planning Project (YZ-11-28).

Conflict of interest

The authors have no financial conflicts of interest.

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Authors and Affiliations

  1. Nanjing Medical University, Nanjing, 210029, China

    Qingquan Luo

  2. Shanghai Lung Tumor Clinical Medical Center, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, 200030, China

    Hao Lin, Xiangyun Ye, Jia Huang & Shun Lu

  3. Department of Thoracic Surgery, Nanjing Medical University Affiliated Cancer Hospital, Nanjing, 210009, Jiangsu, China

    Lin Xu

Authors
  1. Qingquan Luo
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  2. Hao Lin
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  3. Xiangyun Ye
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  4. Jia Huang
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  5. Shun Lu
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  6. Lin Xu
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Corresponding authors

Correspondence to Shun Lu or Lin Xu.

Additional information

Q. Luo and H. Lin contributed equally to the work.

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Luo, Q., Lin, H., Ye, X. et al. Trim44 facilitates the migration and invasion of human lung cancer cells via the NF-κB signaling pathway. Int J Clin Oncol 20, 508–517 (2015). https://doi.org/10.1007/s10147-014-0752-9

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  • DOI: https://doi.org/10.1007/s10147-014-0752-9

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