Skip to main content
SpringerLink
Log in

MiR-4652-5p Targets RND1 to Regulate Cell Adhesion and Promote Lung Squamous Cell Carcinoma Progression

  • Original Article
  • Published:
Applied Biochemistry and Biotechnology Aims and scope Submit manuscript

Abstract

Lung squamous cell carcinoma (LUSC) is one subtype of non-small-cell lung cancer, whose pathogenesis has not been fully understood. Exploring molecular mechanisms of LUSC helps a lot with the development of LUSC novel therapy. Hence, our study aims to investigate novel molecular mechanisms. Differentially expressed miRNAs and mRNAs were acquired from The Cancer Genome Atlas database. A series of assays were applied to test cell functions, including qRT-PCR to analyze RND1 and miR-4652-5p expression, dual-luciferase reporter gene assay to verify the targeting relationship between these two genes, cell counting kit-8 and colony formation assays to evaluate the ability of LUSC cells to proliferate, transwell to examine the migratory and invasive abilities, and western blot to test expression of RND1 and cell adhesion-related proteins. RND1 was lowly expressed while miR-4652-5p was highly expressed in LUSC cells. The correlation between these two genes was significantly negative and miR-4652-5p could downregulate RND1 expression. Additionally, cellular function assays validated that RND1 suppressed LUSC cells to proliferate, migrate, and invade. Besides, this gene might also affect cell adhesion. Furthermore, rescue assay suggested that miR-4652-5p downregulated RND1 expression to promote the progression of LUSC cells. Together, miR-4652-5p targeted RND1 to modulate cell adhesion and the progression of LUSC cells.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Data Availability

The data and materials in the current study are available from the corresponding author on reasonable request.

References

  1. Conti, L., & Gatt, S. (2018). Squamous-cell carcinoma of the lung. New England Journal of Medicine, 379, e17. https://doi.org/10.1056/NEJMicm1802514

    Article  PubMed  Google Scholar 

  2. Gao, M., Kong, W., Huang, Z. & Xie, Z. (2020) Identification of key genes related to lung squamous cell carcinoma using bioinformatics analysis. International Journal of Molecular Sciences 21, https://doi.org/10.3390/ijms21082994.

  3. Xu, F., Zhang, H., Chen, J., Lin, L., & Chen, Y. (2020). Immune signature of T follicular helper cells predicts clinical prognostic and therapeutic impact in lung squamous cell carcinoma. International Immunopharmacology, 81, 105932. https://doi.org/10.1016/j.intimp.2019.105932

    Article  CAS  PubMed  Google Scholar 

  4. Mouly, L. et al. (2019) The RND1 small GTPase: Main functions and emerging role in oncogenesis. International Journal of Molecular Sciences 20, https://doi.org/10.3390/ijms20153612.

  5. Okada, T., et al. (2015). The Rho GTPase Rnd1 suppresses mammary tumorigenesis and EMT by restraining Ras-MAPK signalling. Nature Cell Biology, 17, 81–94. https://doi.org/10.1038/ncb3082

    Article  CAS  PubMed  Google Scholar 

  6. Qin, C. D., et al. (2018). The Rho GTPase Rnd1 inhibits epithelial-mesenchymal transition in hepatocellular carcinoma and is a favorable anti-metastasis target. Cell Death & Disease, 9, 486. https://doi.org/10.1038/s41419-018-0517-x

    Article  CAS  Google Scholar 

  7. Chen, X., Koh, E., Yoder, M., & Gumbiner, B. M. (2009). A protocadherin-cadherin-FLRT3 complex controls cell adhesion and morphogenesis. PLoS ONE, 4, e8411. https://doi.org/10.1371/journal.pone.0008411

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Ogata, S., et al. (2007). TGF-beta signaling-mediated morphogenesis: Modulation of cell adhesion via cadherin endocytosis. Genes & Development, 21, 1817–1831. https://doi.org/10.1101/gad.1541807

    Article  CAS  Google Scholar 

  9. Li, B., et al. (2020). WNT1, a target of miR-34a, promotes cervical squamous cell carcinoma proliferation and invasion by induction of an E-P cadherin switch via the WNT/beta-catenin pathway. Cellular Oncology (Dordrecht), 43, 489–503. https://doi.org/10.1007/s13402-020-00506-8

    Article  CAS  Google Scholar 

  10. Mitra, R., Adams, C. M., Jiang, W., Greenawalt, E., & Eischen, C. M. (2020). Pan-cancer analysis reveals cooperativity of both strands of microRNA that regulate tumorigenesis and patient survival. Nature Communications, 11, 968. https://doi.org/10.1038/s41467-020-14713-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Jiang, C., Hu, X., Alattar, M., & Zhao, H. (2014). miRNA expression profiles associated with diagnosis and prognosis in lung cancer. Expert Review of Anticancer Therapy, 14, 453–461. https://doi.org/10.1586/14737140.2013.870037

    Article  CAS  PubMed  Google Scholar 

  12. Lu, J., et al. (2005). MicroRNA expression profiles classify human cancers. Nature, 435, 834–838. https://doi.org/10.1038/nature03702

    Article  CAS  PubMed  Google Scholar 

  13. Chen, C., Tang, J., Xu, S., Zhang, W., & Jiang, H. (2020). miR-30a-5p inhibits proliferation and migration of lung squamous cell carcinoma cells by targeting FOXD1. BioMed Research International, 2020, 2547902. https://doi.org/10.1155/2020/2547902

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Qiao, G., Wang, H. B., Duan, X. N., & Yan, X. F. (2021). The effect and mechanism of miR-607/CANT1 axis in lung squamous carcinoma. Anti-Cancer Drugs, 32, 693–702. https://doi.org/10.1097/CAD.0000000000001045

    Article  CAS  PubMed  Google Scholar 

  15. Wu, Y., et al. (2020). miR-1301-3p promotes the proliferation and migration of lung cancer cells via direct repression of polymerase I and transcript release factor. Oncology Letters, 20, 286. https://doi.org/10.3892/ol.2020.12149

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Robinson, M. D., McCarthy, D. J., & Smyth, G. K. (2010). edgeR: A Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics, 26, 139–140. https://doi.org/10.1093/bioinformatics/btp616

    Article  CAS  PubMed  Google Scholar 

  17. Boyrie, S., et al. (2018). RND1 regulates migration of human glioblastoma stem-like cells according to their anatomical localization and defines a prognostic signature in glioblastoma. Oncotarget, 9, 33788–33803. https://doi.org/10.18632/oncotarget.26082

    Article  PubMed  PubMed Central  Google Scholar 

  18. Cheng, Z., et al. (2019). circTP63 functions as a ceRNA to promote lung squamous cell carcinoma progression by upregulating FOXM1. Nature Communications, 10, 3200. https://doi.org/10.1038/s41467-019-11162-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Fan, X., et al. (2020). Long non-coding RNA LINC01116 regulated miR-744-5p/SCN1B axis to exacerbate lung squamous cell carcinoma. Cancer Biomarkers, 28, 473–482. https://doi.org/10.3233/CBM-190945

    Article  CAS  PubMed  Google Scholar 

  20. Wang, Z., et al. (2019). Identification of seven-gene signature for prediction of lung squamous cell carcinoma. Oncotargets and Therapy, 12, 5979–5988. https://doi.org/10.2147/OTT.S198998

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Shen, L., et al. (1842). Overexpression of Oct4 suppresses the metastatic potential of breast cancer cells via Rnd1 downregulation. Biochimica et Biophysica Acta, 2087–2095, 2014. https://doi.org/10.1016/j.bbadis.2014.07.015

    Article  CAS  Google Scholar 

  22. Yang, C., Dou, R., Yin, T., & Ding, J. (2020). MiRNA-106b-5p in human cancers: Diverse functions and promising biomarker. Biomedicine & Pharmacotherapy, 127, 110211. https://doi.org/10.1016/j.biopha.2020.110211

    Article  CAS  Google Scholar 

  23. Wu, C., et al. (2020). Two miRNA prognostic signatures of head and neck squamous cell carcinoma: A bioinformatic analysis based on the TCGA dataset. Cancer Medicine, 9, 2631–2642. https://doi.org/10.1002/cam4.2915

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Li, Y., et al. (2020). SPEN induces miR-4652-3p to target HIPK2 in nasopharyngeal carcinoma. Cell Death & Disease, 11, 509. https://doi.org/10.1038/s41419-020-2699-2

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Cardiac Thoracic Surgery, Hunan Provincial People’s Hospital (The First-Affiliated Hospital of Hunan Normal University), No.61, Jiefang West Road, Furong District, Changsha, 410000, China

    Yafu Zhou, Jianhua Yan, Huiguo Chen, Wenwu Zhou, Guohua Xiao, Haoyu Zou & Jinsong Yang

Authors
  1. Yafu Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jianhua Yan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Huiguo Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Wenwu Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Guohua Xiao
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Haoyu Zou
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jinsong Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Y. Z. and S. Y. contributed to the study design. J. Y. and H. C. conducted the literature search. W. Z. and G. X. acquired the data. H. Z. wrote the article. Y. Z. performed the data analysis and drafted. S. Y. revised the article. All the authors gave the final approval of the version to be submitted.

Corresponding author

Correspondence to Jinsong Yang.

Ethics declarations

Ethics Approval and Consent to Participate

Not applicable.

Competing Interest

The authors declare no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhou, Y., Yan, J., Chen, H. et al. MiR-4652-5p Targets RND1 to Regulate Cell Adhesion and Promote Lung Squamous Cell Carcinoma Progression. Appl Biochem Biotechnol 194, 3031–3043 (2022). https://doi.org/10.1007/s12010-022-03897-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12010-022-03897-6

Keywords

Search

Navigation