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MicroRNA-338-5p plays a tumor suppressor role in glioma through inhibition of the MAPK-signaling pathway by binding to FOXD1

  • Original Article – Cancer Research
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

A Correction to this article was published on 19 November 2021

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Abstract

Purpose

MicroRNAs (miRs) play an important role in many cancers and can affect cancer cell behavior, including glioma. This study aims at investigating the effects of miR-338-5p on the senescence, migration, invasion, and apoptosis of glioma cells via MAPK-signaling pathway by binding to FOXD1.

Methods

Gene expression microarray analysis was performed to screen differentially expressed miRNAs associated with glioma. Glioma tissues and adjacent tissues were collected. siRNA, mimic, and inhibitor were introduced for investigating the tumor suppressor role of miR-338-5p in glioma. Proliferation, migration, invasion, senescence, cell-cycle distribution, and apoptosis after transfection were detected by MTT assay, scratch test, Transwell assay, β-galactosidase staining, and flow cytometry, respectively.

Results

FOXD1 was identified as the up-regulated gene in glioma based on microarray data of GSE65626. FOXD1 was the target gene of miR-338-5p. Glioma tissues had increased expression of FOXD1, MEK-2, ERK-1, DAF, PCNA, and Bcl-2, and decreased expression of miR-338-5p and Bax. In cell experiments, after transfected with overexpressed miR-338-5p, higher expression of miR-338-5p, Bax, CD133, ZEB1, SOX2, SNAI1, and MMP2, but lower expression of FOXD1, MEK-2, ERK-1, Bcl-2, DAF, and PCNA were found accompanied with weaker proliferation, migration and invasion as well as stemness abilities but stronger senescence and higher apoptosis rate.

Conclusion

We found that overexpression of miR-338-5p suppresses glioma cell proliferation, migration, and invasion and accelerates its senescence and apoptosis by decreasing FOXD1 expression via inhibition of activation of MAPK-signaling pathway.

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Acknowledgements

We would like to acknowledge the helpful comments on this paper received from our reviewers.

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Authors and Affiliations

  1. Department of Neurosurgery, Yuquan Hospital, Tsinghua University, No. 5 Shijingshan Road, Shijingshan District, Beijing, 100040, People’s Republic of China

    Xin-Long Ma, Jin Zhu, Bin Luo & Yu-Qi Zhang

  2. Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China

    Feng Shang

  3. Department of Ophthalmology, Peking University Third Hospital, Beijing, 100191, People’s Republic of China

    Wei Ni

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  1. Xin-Long Ma
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  2. Feng Shang
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  3. Wei Ni
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  4. Jin Zhu
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Contributions

All the authors contributed to the design and coordination of the study and data collection, prepared the manuscript, and reviewed and approved the final version of the article.

Corresponding author

Correspondence to Yu-Qi Zhang.

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Conflict of interest

The authors disclose no potential conflicts of interest.

Ethical approval

The study was conducted in strict accordance with the ethical standards of the national ethics committee, and written informed consent was obtained from each participant.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Additional information

The original online version of this article was revised due to correction in figures 8 and 10.

Electronic supplementary material

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432_2018_2745_MOESM1_ESM.eps

Supplementary Fig 1 si-FOXD1-3 is selected for further experiments. Note: *, p < 0.05 compared with the NC group; #, p < 0.05, compared with the blank and NC groups. The data were analyzed by paired t test. n = 130; FOXD1, forkhead box D1; NC, negative control (EPS 355 KB)

432_2018_2745_MOESM2_ESM.eps

Supplementary Fig 2 Overexpressed miR-338-5p or siRNA-FOXD1 could inhibit the stemness and invasiveness of tumor cells. Note: *, p < 0.05 compared with the control group; #, p < 0.05, compared with the blank and NC groups. The data were analyzed by paired t test. n = 130; miR-338-5p, microRNA-338-5p; FOXD1, forkhead box D1; NC, negative control (EPS 434 KB)

432_2018_2745_MOESM3_ESM.eps

Supplementary Fig 3 More cells arrested in G0/G1 phase after transfected with overexpressed miR-338-5p. Note: A, cell-cycle distribution after transfection; B, histogram of cell cycle; *, p < 0.05 compared with the control group; #, p < 0.05, compared with the blank and NC groups. The data were analyzed by paired t test. n = 130; miR-338-5p, microRNA-338-5p; NC, negative control (EPS 645 KB)

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Ma, XL., Shang, F., Ni, W. et al. MicroRNA-338-5p plays a tumor suppressor role in glioma through inhibition of the MAPK-signaling pathway by binding to FOXD1. J Cancer Res Clin Oncol 144, 2351–2366 (2018). https://doi.org/10.1007/s00432-018-2745-y

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