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The role of miRNA-377 as a tumor suppressor in lung cancer by negative regulation of genes belonging to ErbB signaling pathway

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Abstract

Background

The ErbB signaling pathway plays important role in the pathogenesis of lung cancer. We explored the role of miRNA-377 as a tumor suppressor in NSCLC through silencing of some genes in the ErbB pathway.

Methods and Results

The targeting effect of miRNA-377 on EGFR, MAPK1, ABL2, and PAK2 was evaluated. The expression levels of these genes and miRNA-377 were surveyed in NSCLC and normal human tissues, Calu-6, and A549 cells. Real-time PCR was used to figure out whether miRNA-377 could decrease the target genes mRNAs in transfected lung cancer cell lines. The effects of miRNA-377 on apoptosis cell and proliferation were analyzed. We showed that miRNA-377 targets EGFR, MAPK1, and PAK2 mRNAs in in-silico and luciferase reporter assay. The expression of miRNA-377 was significantly downregulated in human NSCLC tissues, Calu-6 and A549 cells compared to their controls. We observed a negative correlation between EGFR, MAPK1, PAK2, and miRNA-377 expression in human NSCLC tissues. A significant reduction in EGFR, MAPK1, and PAK2 mRNA levels was detected, following miRNA-377 transfection in Calu-6 and A549 cells. The higher levels of miRNA-377 in Calu-6, and A549 cells induced apoptosis and reduced proliferation, significantly.

Conclusions

All these data reveal that miRNA-377 functions as a tumor suppressor in NSCLC and may serve as a potential therapeutic target for the treatment of NSCLC.

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Data availability

The authors confirm that the data supporting the findings of this study are available.

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Acknowledgements

We thank the patients and clinicians contributing to this study. In addition, we thank Virology Department staffs for providing us the equipment. This work was supported by the Pasteur Institute of Iran. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Author notes

  1. Saba Hashemi, Naghmeh Yari have contributed equally to this work.

Authors and Affiliations

  1. Molecular Medicine Department, Biotechnology Research Center, Pasteur Institute of Iran, 69th Pasteur Street, Kargar Avenue, Tehran, Iran

    Saba Hashemi, Naghmeh Yari, Reza Mahdian, Morteza Karimi, Sirous Zeinali & Masoumeh Azizi

  2. Department of Mycobacteriology and Pulmonary Research, Pasteur Institute of Iran, Tehran, Iran

    Fatemeh Rahimi Jamnani

  3. Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran

    Mohammad Hesam Rafiee

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  1. Saba Hashemi
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Contributions

MA and SZ designed the study. NY, SH, FRJ, MK and MHR carried out the experiments. MA, FRJ, SH, NY and RM collected and analyzed the data. SH and MA wrote the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Masoumeh Azizi.

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Conflict of interest

All authors declare that they have no conflict of interest.

Ethical approval

The present study was conducted under the instructions accepted by the Ethics Committee of Pasteur Institute of Iran, written informed consent to participate, and consent to publish forms was obtained from all participants involved in the present study. This material is the authors' own original work, which has not been previously published elsewhere. The paper is not currently being considered for publication elsewhere. The paper reflects the authors' own research and analysis in a truthful and complete manner.

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Hashemi, S., Yari, N., Rahimi Jamnani, F. et al. The role of miRNA-377 as a tumor suppressor in lung cancer by negative regulation of genes belonging to ErbB signaling pathway. Mol Biol Rep 49, 85–95 (2022). https://doi.org/10.1007/s11033-021-06844-6

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  • DOI: https://doi.org/10.1007/s11033-021-06844-6

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