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TRIM38 suppresses migration, invasion, metastasis, and proliferation in non-small cell lung cancer (NSCLC) via regulating the AMPK/NF-κB/NLRP3 pathway

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Abstract

Accumulating data have revealed the pivotal function of tripartite motif protein 38 (TRIM38) in tumors. In view of this, this investigation aims to explore the function and potential mechanism of TRIM38 in non-small cell lung cancer (NSCLC). A xenotypic tumor model was established in vivo by subcutaneously injecting NSCLC cells (2 × 106 cells) in tail vein of each mouse. Relative expression of TRIM38 mRNA was detected via quantitative real-time polymerase chain reaction (qRT-PCR). For exploring the role of TRIM38 in vivo and in vitro, mice or NSCLC cells were divided into two groups: the vector group and the TRIM38 overexpression group. Also, protein expression levels of TRIM38, Vimentin, E-cadherin, and N-cadherin were determined using western blotting and immunohistochemistry staining. Tumor nodules of mouse lung tissues were assessed via performing H&E staining. Moreover, proliferation of NSCLC cells was evaluated through colony formation and CCK-8 assays. Further, migration and invasion of NSCLC cells were assessed through wound healing and transwell assays. Protein levels of pathway-related proteins including p-p65, p65, IκB, p-IκB, p-AMPK, AMPK, and NLRP3 were examined through western blotting analysis. Tumor lung tissues of mice and NSCLC cells showed low protein and mRNA expression of TRIM38. Functionally, up-regulation of TRIM38 reduced the number of tumor nodules and suppressed epithelial-to-mesenchymal transition (EMT) in lung tissues of mice. Furthermore, up-regulation of TRIM38 in NSCLC cells inhibited migration, invasion, EMT, and proliferation. With respect to the mechanism, in vivo experiments, the inhibitory effects of TRIM38 overexpression on tumor nodules, and EMT were reversed by AMPK inhibitor. In vitro experiments, TRIM38 overexpression caused down-regulation of p-IκB and p-p65 as well as up-regulation of p-AMPK. The inhibitory effects of TRIM38 overexpression on migration, proliferation, invasion, and EMT of NSCLC cells were reversed by overexpression of NLRP3. Concurrently, AMPK inhibitor enhanced the TRIM38-overexpressed NSCLC cell’s abilities in migration, clone formation, invasion, and proliferation. TRIM38 regulated the AMPK/NF-κB/NLRP3 pathway to suppress the NSCLC’s progression and development.

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Data availability

The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.

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Authors and Affiliations

  1. Department of Thoracic Surgery, China Aerospace Science & Industry Corporation 731 Hospital, No. 3, Zhen Gang Nan Li, Yun Gang, Feng Tai District, Beijing, 100074, China

    Kaihua Zhang, Guihu Lin, Zhenkai Nie, Shan Jin, Xiaohan Bing, Zhantao Li & Mingru Li

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  1. Kaihua Zhang
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  2. Guihu Lin
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  3. Zhenkai Nie
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  4. Shan Jin
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  5. Xiaohan Bing
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  6. Zhantao Li
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  7. Mingru Li
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Contributions

KHZ and MRL designed the study; GHL, ZKN, and SJ collected the data; XHB, ZTL, and MRL analyzed the data. All authors read and approved the final manuscript.

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Correspondence to Mingru Li.

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For conducting animal experiments, Institutional Animal Care and Use Committee’s guidelines from Beijing Viewsolid Biotechnology Co. LTD were followed (VS212601456).

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Zhang, K., Lin, G., Nie, Z. et al. TRIM38 suppresses migration, invasion, metastasis, and proliferation in non-small cell lung cancer (NSCLC) via regulating the AMPK/NF-κB/NLRP3 pathway. Mol Cell Biochem (2023). https://doi.org/10.1007/s11010-023-04823-y

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