Circular RNA circAGAP1 promotes sunitinib sensitivity in renal cell carcinoma via sponging multiple PDGFR-targeted

Q I Lv1, Gangmin Wang2, Y I Hong1

  • 1Imaging Department, Tongji Hospital, Tongji University School of Medicine, Shanghai, 200065, China.

Oncology Research
|January 27, 2025
PubMed
Abstract

Insights

Circular RNA circAGAP1 enhances sunitinib sensitivity in clear cell renal cell carcinoma (ccRCC). This finding suggests circAGAP1 is a potential biomarker and therapeutic target for ccRCC treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Sunitinib resistance is a significant clinical challenge in advanced renal cell carcinoma (RCC).
  • Previous studies identified circAGAP1 upregulation in clear cell RCC (ccRCC) associated with poor prognosis.
  • The role of circAGAP1 in sunitinib resistance in ccRCC was previously unclear.

Purpose of the Study:

  • To investigate the role of circAGAP1 in sunitinib resistance in clear cell renal cell carcinoma.
  • To elucidate the underlying molecular mechanisms of circAGAP1 in ccRCC sunitinib resistance.
  • To evaluate circAGAP1 as a potential biomarker and therapeutic target for ccRCC.

Main Methods:

  • Bioinformatics analysis of public databases to identify circAGAP1 binding targets.
  • In vitro assays (qPCR, CCK-8, migration, apoptosis, colony formation) to assess circAGAP1 effects on ccRCC cells.
  • RNA immunoprecipitation, dual-luciferase reporter, and FISH assays to explore molecular mechanisms.

Main Results:

  • circAGAP1 expression was higher in sunitinib-sensitive ccRCC cells and inhibited proliferation, clonogenesis, and migration post-sunitinib treatment.
  • circAGAP1 acts as a microRNA sponge, suppressing miR-149-5p, miR-455-5p, and miR-15a-5p to regulate sunitinib target platelet-derived growth factor receptor.
  • Overexpression of these three miRNAs reversed circAGAP1-mediated sunitinib sensitivity.

Conclusions:

  • circAGAP1 demonstrates a role in enhancing sunitinib sensitivity in ccRCC.
  • circAGAP1 functions by sponging specific microRNAs, impacting ccRCC cell behavior under sunitinib treatment.
  • circAGAP1 is a potential predictive biomarker for sunitinib sensitivity and a therapeutic target in ccRCC.

Related Concept Videos

mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
3.7K
The Retinoblastoma Gene01:20

The Retinoblastoma Gene

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
4.0K
MicroRNAs01:22

MicroRNAs

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns—non-coding regions of a gene—or intergenic regions—stretches of DNA present between genes. Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After...
21.2K
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
4.6K
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.4K
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
7.4K