CircWDR78 inhibits the development of colorectal cancer by regulating the miR-653-3p/RGS4 axis

Chu Hao1, Yunju Pu1, Jiunian Li1

  • 1Laboratory of Cancer Epigenetics, Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, 214122, China.

Abstract

Insights

Circular RNA circWDR78 inhibits colorectal cancer (CRC) progression by downregulating miR-653-3p and its target RGS4. Lower circWDR78 expression correlates with CRC advancement, suggesting its potential as a diagnostic and therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • RNA Biology

Background:

  • Colorectal cancer (CRC) presents a significant global health challenge due to increasing mortality rates.
  • Low diagnostic accuracy, poor prognosis, and high recurrence contribute to CRC's high mortality.
  • Circular RNAs (circRNAs), noncoding RNA molecules with a closed-loop structure, are increasingly recognized for their role in tumor progression.

Purpose of the Study:

  • To investigate the role of circWDR78 in colorectal cancer (CRC).
  • To explore the molecular mechanisms underlying circWDR78's function in CRC.
  • To identify potential diagnostic and therapeutic targets for CRC intervention.

Main Methods:

  • Verification of circWDR78's circular structure using Actinomycin D and RNA digestion experiments.
  • In vitro functional assays to evaluate proliferation and motility.
  • RNA-sequencing to identify regulated pathways and genes.
  • Luciferase and qRT-PCR assays to confirm the interaction between circWDR78, miR-653-3p, and RGS4.

Main Results:

  • circWDR78 expression is significantly lower in colorectal cancer tissues.
  • Downregulation of circWDR78 correlates with increased proliferation, colony formation, and cell motility.
  • circWDR78 acts as a molecular sponge for miR-653-3p.
  • RGS4 is identified as a novel downstream target of miR-653-3p.

Conclusions:

  • circWDR78 functions as a tumor suppressor in colorectal cancer.
  • The circWDR78/miR-653-3p/RGS4 axis represents a novel regulatory pathway in CRC progression.
  • circWDR78 holds potential as a biomarker and therapeutic target for colorectal cancer.

Related Concept Videos

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 the pre-miRNA...
3.0K
Canonical Wnt Signaling Pathway02:54

Canonical Wnt Signaling Pathway

The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which...
8.7K
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
Experimental RNAi02:15

Experimental RNAi

RNA interference (RNAi) is a cellular mechanism that inhibits gene expression by suppressing its transcription or activating the RNA degradation process. The mechanism was discovered by Andrew Fire and Craig Mello in 1998 in plants. Today, it is observed in almost all eukaryotes, including protozoa, flies, nematodes, insects, parasites, and mammals. This precise cellular mechanism of gene silencing has been developed into a technique that provides an efficient way to identify and determine the...
6.0K
Non-Canonical Wnt Signaling Pathways01:41

Non-Canonical Wnt Signaling Pathways

Wnt is a zygotic effect gene that is expressed during very early embryonic development. It regulates various processes in animals starting from early development through the adult stage, such as organogenesis in the embryo and maintenance of neuronal and blood stem cells. Wnt proteins can induce a wide variety of intracellular pathways depending upon the specific abilities of different Wnt ligands to form a complex with shared and cognate receptors in the presence of different co-receptors. The...
7.2K
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