hsa_circ_0003596, as a novel oncogene, regulates the malignant behavior of renal cell carcinoma by modulating

QingZhi Xie1, FuQiang Qin1, LiHui Luo2

  • 1Department of Urology Surgery, The First Affiliated Hospital of Shaoyang University, Shaoyang, 422000, Hunan, China.

PubMed
Abstract

Insights

Circular RNA circCOL5A1 promotes renal cell carcinoma (RCC) by enhancing glycolysis. Silencing circCOL5A1 inhibits tumor growth and malignancy, offering a potential therapeutic target for RCC treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Renal cell carcinoma (RCC) is a significant health concern.
  • Understanding the molecular mechanisms driving RCC progression is crucial for developing effective treatments.
  • Dysregulation of circular RNAs and metabolic pathways like glycolysis are implicated in various cancers.

Purpose of the Study:

  • To investigate the role of hsa_circ_0003596 (circCOL5A1) in renal cell carcinoma (RCC).
  • To elucidate the involvement of glycolysis-focused mechanisms in circCOL5A1-mediated RCC progression.
  • To explore the circCOL5A1/miR-370-5p/PRKCSH regulatory axis in RCC.

Main Methods:

  • Quantification of circCOL5A1, miR-370-5p, and PRKCSH expression in RCC tissues and cell lines using RT-qPCR and Western blot.
  • Functional assays including colony formation, EdU, Transwell, and flow cytometry to assess cell proliferation, invasion, migration, and apoptosis.
  • Glycolysis evaluation through glucose consumption, lactate, ATP production, and key glycolytic enzyme expression (HK2, PKM2).
  • In vivo studies involving circCOL5A1 knockdown in animal models.
  • Luciferase reporter and RIP assays to confirm the ceRNA network.

Main Results:

  • circCOL5A1 and PRKCSH were upregulated, while miR-370-5p was downregulated in RCC.
  • circCOL5A1 knockdown suppressed RCC cell proliferation, invasion, migration, and glycolysis, while enhancing apoptosis.
  • circCOL5A1 acts as a sponge for miR-370-5p, and miR-370-5p targets PRKCSH.
  • Overexpression of miR-370-5p counteracted the pro-tumor effects of circCOL5A1, and PRKCSH overexpression reversed the anti-tumor effects of circCOL5A1 silencing.
  • Silencing circCOL5A1 inhibited tumor growth and glycolysis in vivo.

Conclusions:

  • circCOL5A1 promotes the malignant behavior of RCC by modulating glycolysis.
  • The circCOL5A1/miR-370-5p/PRKCSH axis plays a critical role in RCC pathogenesis.
  • circCOL5A1 represents a potential therapeutic target for renal cell carcinoma.

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