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PLEK2 promotes the proliferation and migration of non-small cell lung cancer cells in a BRD4-dependent manner

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Abstract

Background

It has been reported that Pleckstrin 2 (PLEK2) acts as an oncogene in non-small cell lung cancer (NSCLC). Bromodomain containing protein 4 (BRD4), an important transcriptional regulator of tumorigenesis, has been shown to play a key role in NSCLC. However, whether BRD4 regulates the transcription of PLEK2 and further promotes the proliferation and migration of NSCLC remains unknown.

Methods and results

In this study, we performed western blotting, real-time quantitative polymerase chain reaction, immunofluorescence, cell scratch wound assay and chromatin immunoprecipitation. According to these results, we found that PLEK2 plays a tumor‑promoting role in NSCLC via the PI3K/AKT signaling pathway. Moreover, BRD4 expression is significantly upregulated in NSCLC cell lines and suppression of BRD4 expression by siBRD4 and JQ-1 inhibits NSCLC cell lines proliferation and migration. Prominently, we first confirmed that BRD4 binds to the promoter region of the PLEK2 gene, which explains the mechanism by which BRD4 regulates the transcription of PLEK2 gene from the perspective of epigenetics.

Conclusions

The present study suggested that PLEK2 promotes the proliferation and migration of NSCLC in a BRD4-dependent manner and provided key insights into the potential avenues for preventing and treating NSCLC.

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Data availability

All data used or analyzed during the current study are included in the manuscript submission.

Code availability

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Funding

This research was supported by the Zhejiang Science and Technology Plan of Traditional Chinese Medicine under Grant No. 2022ZA055.

Author information

Authors and Affiliations

  1. The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou, China

    Tiantian Cai, Wendong Yao, Zheng Shi & Yi Du

  2. Department of Pharmacy, Jiuting Hospital of Songjiang District, Shanghai, China

    Lei Qiu

  3. School of Pharmacy, Nanjing Medical University, Nanjing, China

    Austin Rui Zhu

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  1. Tiantian Cai
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Contributions

TC, WY, and YD designed and performed experiments, analyzed the data, and wrote the manuscript. LQ and ZS performed experiments and analyzed the data. ARZ, ZS, and YD designed experiments and wrote the manuscript.

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Correspondence to Yi Du.

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Cai, T., Yao, W., Qiu, L. et al. PLEK2 promotes the proliferation and migration of non-small cell lung cancer cells in a BRD4-dependent manner. Mol Biol Rep 49, 3693–3704 (2022). https://doi.org/10.1007/s11033-022-07209-3

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  • DOI: https://doi.org/10.1007/s11033-022-07209-3

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