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High level of LncRNA MAPKAPK5-AS1 predicts poor prognosis and contributes to the malignant proliferation and EMT of non-small cell lung cancer via sponging miR-490-3p from HMGB2

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Abstract

Background

Patients with non-small cell lung cancer (NSCLC) show a low survival rate, owing to the lack of early diagnostic method and high invasiveness. Long non-coding RNA MAPKAPK5-AS1 that regulates tumor genesis and progression through multiple signals, is upregulated and involved in the growth and apoptosis in lung adenocarcinoma (LUAD).

Objective

To investigate whether MAPKAPK5-AS1 affected the malignant progression of NSCLC.

Methods

The levels of MAPKAPK5-AS1, miR-490-3p and HMGB2 in lung cancer were first analyzed through StarBase website, and confirmed by a quantitative reverse transcriptase-PCR (qRT-PCR) assay. The biological functions of NSCLC cells were examined by CCK-8, 5-ethynyl-2ʹ-deoxyuridine (EdU) and flow cytometry assays. The potential binding sequences lncRNA-miRNA and miRNA-mRNA were predicted by StarBase software and verified via dual luciferase reporter experiment. The effects of MAPKAPK5-AS1 on tumor growth were evaluated in a xenografted mice model.

Results

The expression of MAPKAPK5-AS1 was upregulated in tumor tissues from NSCLC patients. Patients with high expression of MAPKAPK5-AS1 had higher tumor size, advanced TNM stage, higher incidence of lymph node and distant metastasis, and shorter overall survival. Knockdown of MAPKAPK5-AS1 inhibited the proliferation, induced apoptosis and blocked epithelial mesenchymal transformation (EMT) of NSCLC cells. Mechanically, MAPKAPK5-AS1 could upregulate the HMGB2 level in NSCLC cells through competitively binding to miR-490-3p. MiR-490-3p inhibitor reversed the roles of MAPKAPK5-AS1 knockdown on tumor cell proliferation, apoptosis and EMT. Also, HMGB2 knockdown suppressed tumor cell malignant phenotypes. Furthermore, interference of MAPKAPK5-AS1 slowed NSCLC tumor growth in vivo.

Conclusion

Knockdown of MAPKAPK5-AS1 inhibited the aggressive tumor phenotypes through miR-490-3p/HMGB2 axis in NSCLC. MAPKAPK5-AS1/miR-490-3p/HMGB2 might be potential biomarkers or therapeutic targets for NSCLC.

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Data availability

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

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Author notes

  1. Jidong Miao and Yang Gao contribute the same to this project.

Authors and Affiliations

  1. Department of Oncology, Zigong Fourth People’s Hospital, No.282, Dangui Street, Ziliujing District, Zigong City, 643000, Sichuan Province, People’s Republic of China

    Jidong Miao, Yang Gao, Wenqiang Guan, Lili Yang, Lun Xu & Wei You

  2. Department of Laboratory Medicine, Zigong Fourth People’s Hospital, Zigong City, Sichuan Province, People’s Republic of China

    Xiaolin Yu

  3. Department of Pathology, Zigong Fourth People’s Hospital, Zigong City, Sichuan Province, People’s Republic of China

    Yong Wang

  4. Department of Radiology, Zigong Fourth People’s Hospital, Zigong City, Sichuan Province, People’s Republic of China

    Ping Jiang

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  1. Jidong Miao
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Contributions

WY: study design and manuscript preparation; JM: experiment performing, data analysis and manuscript preparation; YG and WG: specimen collection and data analysis; XY and YW: study concepts and design; PJ, LY and LX: quality control of data and manuscript review.

Corresponding author

Correspondence to Wei You.

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Conflict of interest

Jidong Miao, Yang Gao, Wenqiang Guan, Xiaolin Yu, Yong Wang, Ping Jiang, Lili Yang, Lun Xu and Wei You declare that they have no conflict of interest.

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The study was approved by Zigong Fourth People’s Hospital and all patients signed informed consent before tissue collection.

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Miao, J., Gao, Y., Guan, W. et al. High level of LncRNA MAPKAPK5-AS1 predicts poor prognosis and contributes to the malignant proliferation and EMT of non-small cell lung cancer via sponging miR-490-3p from HMGB2. Genes Genom 45, 611–625 (2023). https://doi.org/10.1007/s13258-022-01339-5

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