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Updated: Sep 1, 2025

Comparing Metastatic Clear Cell Renal Cell Carcinoma Model Established in Mouse Kidney and on Chicken Chorioallantoic Membrane
05:36

Comparing Metastatic Clear Cell Renal Cell Carcinoma Model Established in Mouse Kidney and on Chicken Chorioallantoic Membrane

Published on: February 8, 2020

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Effect of Extracellular Signal-Regulated Protein Kinase 5 Inhibition in Clear Cell Renal Cell Carcinoma

Hidenori Kanno1, Sei Naito1, Yutaro Obara2

  • 1Department of Urology, Yamagata University Faculty of Medicine, 2-2-2 Iida-Nishi, Yamagata 990-9585, Japan.

International Journal of Molecular Sciences
|August 12, 2022
PubMed

Insights

Extracellular signal-regulating kinase 5 (ERK5) is linked to clear cell renal cell carcinoma (ccRCC) progression. Inhibiting ERK5 shows promise for treating ccRCC by reducing cell proliferation and survival.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Signaling

Background:

  • Extracellular signal-regulating kinase 5 (ERK5) plays a role in cell survival, proliferation, and vascularization.
  • Clear cell renal cell carcinoma (ccRCC) is a significant subtype of kidney cancer.
  • Understanding the role of ERK5 in ccRCC is crucial for developing new therapeutic strategies.

Purpose of the Study:

  • To investigate the expression and functional role of ERK5 in clear cell renal cell carcinoma (ccRCC).
  • To explore the relationship between ERK5 and its regulating micro-RNA, miR-143, in ccRCC.
  • To evaluate the therapeutic potential of targeting ERK5 in ccRCC.

Main Methods:

  • Immunohistochemistry and quantitative reverse transcriptase PCR were used to assess ERK5 and miR-143 expression in ccRCC specimens.
  • In vitro studies involved pharmacologic inhibition of ERK5 (XMD8-92), RNA interference, and pre-miR-143 transduction.
  • In vivo efficacy was evaluated using a subcutaneous xenograft model, alongside Western blotting, MTS assays, and apoptosis assays.

Main Results:

  • Strong ERK5 expression in ccRCC surgical specimens correlated with high grade, high recurrence rates, and poor cancer-specific survival.
  • ERK5 and miR-143 expression levels were significantly correlated, with miR-143 suppressing ERK5 expression.
  • ERK5 inhibition led to increased p21 expression, decreased BCL2, reduced ccRCC and endothelial cell proliferation and survival, and suppressed tumor growth in vivo.

Conclusions:

  • ERK5 expression is regulated by miR-143 in clear cell renal cell carcinoma.
  • Targeting ERK5 with inhibitors like XMD8-92 demonstrates therapeutic potential for ccRCC treatment.
  • ERK5 inhibition offers a promising strategy to reduce ccRCC cell proliferation and enhance survival.
Keywords:
clear cell renal cell carcinomaextracellular signal-regulating kinase 5miR-143

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