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MicroRNA‑21 contributes to renal cell carcinoma cell invasiveness and angiogenesis via the PDCD4/c‑Jun (AP‑1)

Bo Fan1, Yiying Jin1, Hongshuo Zhang2

  • 1Department of Urology, Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China.

International Journal of Oncology
|December 3, 2019
PubMed

Insights

MicroRNA-21 (miR-21) promotes renal cell carcinoma (RCC) migration, invasion, and angiogenesis by targeting programmed cell death protein 4 (PDCD4). Inhibiting miR-21 offers a potential therapeutic strategy for RCC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • MicroRNAs regulate gene expression and are implicated in cancer progression.
  • Programmed cell death protein 4 (PDCD4) is a tumor suppressor and a target of microRNA-21 (miR-21).
  • The specific role of miR-21 in renal cell carcinoma (RCC) migration, invasion, and angiogenesis requires further elucidation.

Purpose of the Study:

  • To investigate the association between miR-21 expression and prognosis in RCC patients.
  • To determine the in vitro effects of miR-21 on RCC cell migration, invasion, and angiogenesis.
  • To elucidate the molecular mechanism by which miR-21 influences RCC progression.

Main Methods:

  • Meta-analysis of 6 studies involving 473 RCC patients.
  • In vitro experiments using RCC cell lines (A498, 786-O) and endothelial cells (HMEC-1).
  • Assessment of gene and protein expression, cell migration, invasion, and tube formation assays.

Main Results:

  • Increased miR-21 expression is significantly associated with poorer prognosis in RCC (HR=1.740).
  • miR-21 inhibition decreased RCC cell migration and invasion, and reduced expression of PDCD4, c-Jun, MMP2, and MMP9.
  • miR-21 inhibition reduced angiogenesis in HMEC-1 cells by affecting angiotensin-1 and VEGF-A, with PDCD4 siRNA showing opposing effects.

Conclusions:

  • miR-21 promotes RCC migration, invasion, and angiogenesis by targeting the PDCD4/c-Jun signaling pathway.
  • miR-21 is a potential biomarker for adverse prognosis in RCC.
  • Targeting miR-21 presents a promising therapeutic avenue for renal cell carcinoma.

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