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TGF‑β1 affects the renal cancer miRNome and regulates tumor cells proliferation

Karolina Hanusek1, Beata Rybicka1, Piotr Popławski1

  • 1Department of Biochemistry and Molecular Biology, Centre of Postgraduate Medical Education, 01‑813 Warsaw, Poland.

International Journal of Molecular Medicine
|February 18, 2022
PubMed

Insights

Transforming growth factor-beta 1 (TGF-β1) influences renal cell carcinoma (RCC) by regulating microRNAs (miRNAs) and messenger RNAs (mRNAs). This study reveals TGF-β1

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Transforming growth factor-beta 1 (TGF-β1) is a cytokine with dual roles in cancer, potentially promoting or inhibiting tumor development.
  • Previous research indicates TGF-β1 regulates microRNAs (miRNAs) implicated in renal cell carcinoma (RCC) progression.

Purpose of the Study:

  • To investigate the comprehensive effects of TGF-β1 on the RCC miRNome.
  • To elucidate the regulatory network of miRNAs and mRNAs influenced by TGF-β1 in RCC.

Main Methods:

  • Analysis of TGF-β1's impact on the global miRNome in renal cell carcinoma.
  • Investigating the regulation of cell proliferation and oncogenic factors like ETS1 by TGF-β1.
  • Examining the expression changes of specific miRNAs (e.g., miR-30c-5p, miR-155-5p) and TGF-β1 pathway components (receptors, SMADs).

Main Results:

  • TGF-β1 modulates a complex miRNA-mRNA network crucial for RCC transformation.
  • TGF-β1 regulates RCC cell proliferation and alters the expression of oncogenes such as ETS1.
  • Specific miRNAs, including miR-30c-5p, miR-155-5p, miR-181a-5p, and miR-181b-5p, are regulated by TGF-β1.
  • A feedback loop involving TGF-β1 receptors, SMADs, and miRNAs was identified.
  • ETS1 exhibits context-dependent roles, acting as an oncogene in clear cell RCC and a tumor suppressor in papillary RCC.

Conclusions:

  • TGF-β1 significantly influences the RCC miRNome and associated mRNA networks.
  • The findings highlight a novel miRNA-mediated feedback mechanism in TGF-β1 signaling within RCC.
  • ETS1's opposing functions in different RCC subtypes underscore the complexity of TGF-β1's role in renal cancer.
Keywords:
TGF‑β1avian erythroblastosis virus E26 (V‑Ets) oncogene homolog‑1bone morphogenetic protein receptor type 2microRNAmicroRNA‑125b‑5pmicroRNA‑155‑5pmicroRNA‑181a‑5pmicroRNA‑181b‑5pmicroRNA‑30c‑5pproliferationrenal cell cancer

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