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

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CircESRP1 inhibits clear cell renal cell carcinoma progression through the CTCF-mediated positive feedback loop

Lin-Jing Gong1,2, Xin-Yuan Wang3, Xu-Dong Yao4

  • 1Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, No 37 Guoxue Alley, 610041, Chengdu, Sichuan, China.

Cell Death & Disease
|November 14, 2021
PubMed

Insights

A novel circular RNA, circESRP1, is downregulated in kidney cancer and inhibits tumor growth. It forms a feedback loop with miR-3942 and CTCF, impacting cell function and potentially offering new therapeutic targets for renal cell carcinoma.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Circular RNAs (circRNAs) are implicated in human diseases, but their role in renal cell carcinoma (RCC) progression is not fully understood.
  • Understanding the molecular mechanisms of circRNAs in RCC is crucial for developing new therapeutic strategies.

Purpose of the Study:

  • To identify and characterize a novel circRNA, circESRP1, involved in the progression of clear cell renal cell carcinoma (ccRCC).
  • To elucidate the molecular mechanism by which circESRP1 regulates ccRCC progression, including its interactions with other molecules and its role in a feedback loop.

Main Methods:

  • Identification of circESRP1 from the ESRP1 gene locus.
  • Analysis of circESRP1 expression levels in ccRCC tissues and cell lines.
  • In vivo experiments using xenograft models.
  • RNA pull-down, RIP, and dual-luciferase reporter assays to confirm molecular interactions.
  • Investigation of the circESRP1/miR-3942/CTCF feedback loop and its effect on c-Myc-mediated EMT.

Main Results:

  • circESRP1 expression is lower in ccRCC tissues and inversely correlated with tumor size, TNM stage, and metastasis.
  • circESRP1 expression positively correlates with CTCF and negatively with miR-3942 in ccRCC tissues.
  • Overexpression of circESRP1 represses tumor growth and inhibits c-Myc-mediated EMT progression in vivo.
  • circESRP1 acts as a sponge for miR-3942, and CTCF promotes circESRP1 transcription, forming a positive feedback loop.
  • The circESRP1/miR-3942/CTCF feedback loop regulates ccRCC cell functions via c-Myc mediated EMT.

Conclusions:

  • circESRP1 plays a tumor-suppressive role in ccRCC.
  • A novel circRNA-mediated positive feedback loop (circESRP1/miR-3942/CTCF) regulates ccRCC progression.
  • This signaling axis represents a potential therapeutic target for ccRCC treatment.

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