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Can increased expression of miR-Let-7c reduce the transition potential of high-grade urothelial carcinoma?

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Abstract

Background

Bladder cancer is the leading transitional cell carcinoma affecting men and women with high morbidity and mortality rates, justifying the need to develop new molecular target therapies using microRNAs. This study aimed to evaluate the behavior of the T24 cell line after transfection with miR-Let-7c precursor mimic through invasion, migration, apoptosis, and cell cycle assays.

Methods and results

T24 cell was transfected with the Let-7c mimic and its respective control and evaluated after 24 h. The expression levels of miR-Let-7c were analyzed by qPCR. We performed wound healing, Matrigel and flow cytometry, apoptosis, and cell cycle assays to determine its effect on cellular processes. Cells transfected with miR-Let-7c showed increased apoptosis rates (p = 0.019), decreased migration 24 h (p = 0.031) and 48 h (p = 0.0006), invasion potential (p = 0.0007), and cell proliferation (p = 0.002).

Conclusions

Our results demonstrate that miR-Let-7c can act in different pathways of the carcinogenic cellular processes of muscle-invasive urothelial carcinoma cells, inhibiting cell proliferation and increasing apoptosis levels, consequently limiting their invasion potential. However, further studies should be carried out better to elucidate this microRNA’s role in high-grade urothelial carcinomas and unveil which targets this microRNA may present, which are intrinsically related to the cancer survival pathways.

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Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author on request. All datasets generated for this study are included in the article.

Code availability

Not applicable.

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Acknowledgements

To the Fundação Faculdade de Medicina for the institutional Grant awarded (#94180) to the Laboratório de Investigação Médica da disciplina de Urologia (LIM55).

Funding

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Authors and Affiliations

  1. Laboratorio de Investigação Médica 55 (LIM55), Faculdade de Medicina, Hospital das Clinicas HCFMUSP, Universidade de Sao Paulo, São Paulo, SP, Brazil

    Paulo Ricardo da Silva Gomes, Patricia Candido, Vitória Ghazarian, Juliana A. Camargo, Vanessa R. Guimarães, Poliana Romão, Iran A. Silva, Miguel Srougi, Kátia R. Leite, Sabrina T. Reis, Ruan Pimenta & Nayara Izabel Viana

  2. Faculdade de Medicina, Universidade Federal do Pará, Belém, PA, Brazil

    Paulo Ricardo da Silva Gomes

  3. Laboratory of Renal Physiology, Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, São Paulo, Brazil

    Guilherme L. Gonçalves

  4. D’Or Institute for Research and Education (IDOR), São Paulo, Brazil

    Miguel Srougi & Ruan Pimenta

  5. Uro-Oncology Group, Urology Department, University of Sao Paulo Medical School and Institute of Cancer Estate of Sao Paulo (ICESP), São Paulo, Brazil

    William C. Nahas

  6. Universidade do Estado de Minas Gerais - UEMG, Passos, MG, Brazil

    Nayara Izabel Viana

Authors
  1. Paulo Ricardo da Silva Gomes
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  2. Patricia Candido
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  3. Vitória Ghazarian
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  4. Juliana A. Camargo
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  5. Vanessa R. Guimarães
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  6. Guilherme L. Gonçalves
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  7. Poliana Romão
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  8. Iran A. Silva
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  9. Miguel Srougi
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  10. William C. Nahas
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  11. Kátia R. Leite
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  12. Sabrina T. Reis
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  13. Ruan Pimenta
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  14. Nayara Izabel Viana
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Contributions

All authors discussed the results, revised the manuscript draft, and contributed: PRdSG wrote the manuscript and performed the in vitro experiments. PC contributed to the study design and performed the in vitro experiments. VG performed the in vitro experiments. JAC contributed to in vitro experiments. VRG contributed to in vitro experiments. GLG contributed to in vitro experiments, PR contributed to in vitro experiments. IAS contributed to intellectual input. MS supervised the experiments and intellectual information. WCN supervised the experiments and intellectual input. KRL supervised the experiments, contributed to the study design and intellectual input. STR supervised the experiments, contributed to the study design, intellectual input, contributed to statistical analysis. RP contributed to the study design, intellectual input, to statistical analysis assisted in drafting and critical reading. NIV contributed to the study design, supervised the experiments, intellectual input, to statistical analysis assisted in drafting and critical reading.

Corresponding author

Correspondence to Nayara Izabel Viana.

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Supplementary material 1 STR profile reports (PDF 139.0 kb)

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da Silva Gomes, P.R., Candido, P., Ghazarian, V. et al. Can increased expression of miR-Let-7c reduce the transition potential of high-grade urothelial carcinoma?. Mol Biol Rep 48, 7947–7952 (2021). https://doi.org/10.1007/s11033-021-06825-9

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  • DOI: https://doi.org/10.1007/s11033-021-06825-9

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