Related Experiment Video

Updated: Jul 3, 2025

In Vitro Cultivation Techniques for Modeling Liver Organogenesis, Building Assembloids, and Designing Synthetic Tissues using Human Cell Lines
08:50

In Vitro Cultivation Techniques for Modeling Liver Organogenesis, Building Assembloids, and Designing Synthetic Tissues using Human Cell Lines

Published on: April 18, 2025

395

Integrated Multiomics Reveals Silencing of has_circ_0006646 Promotes TRIM21-Mediated NCL Ubiquitination to Inhibit

Xin Hu1,2,3, Guanrong Chen4, Yingchen Huang4

  • 1Zhejiang University School of Medicine, Hangzhou, 310058, China.

Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|February 15, 2024
PubMed

Insights

A novel circular RNA, circ0006646, promotes hepatocellular carcinoma (HCC) metastasis by stabilizing nucleolin (NCL). Targeting circ0006646 offers a potential therapeutic strategy for HCC treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Circular RNAs (circRNAs) are increasingly recognized for their roles in cancer progression.
  • Post-translational modification of RNA-binding proteins (RBPs) by circRNAs is implicated in hepatocellular carcinoma (HCC) metastasis.
  • The precise mechanisms and therapeutic potential of circRNA-RBP interactions in HCC require further elucidation.

Purpose of the Study:

  • To investigate the regulatory network of circRNAs and RBPs in HCC metastasis using a multi-omics approach.
  • To identify and characterize novel circRNAs involved in HCC progression.
  • To explore the therapeutic significance of identified circRNAs in HCC.

Main Methods:

  • Multi-omics profiling to analyze circRNA and RBP regulatory networks.
  • In vivo metastasis assays to evaluate the functional role of circRNAs.
  • Biochemical assays to elucidate the molecular mechanism of circRNA-mediated protein regulation.
  • Patient-derived tumor xenograft and lentivirus injection models to assess therapeutic potential.

Main Results:

  • Has_circ_0006646 (circ0006646), a previously unreported circRNA in HCC, is associated with poor prognosis.
  • Silencing circ0006646 significantly inhibits HCC metastasis in vivo.
  • Circ0006646 stabilizes nucleolin (NCL) by preventing its interaction with the E3 ligase tripartite motif-containing 21, thereby reducing proteasomal degradation.
  • NCL dysregulation affects downstream signaling pathways, including p53 translation inhibition.
  • Therapeutic interventions targeting circ0006646 demonstrated potential in preclinical models.

Conclusions:

  • This study reveals an integrated multi-omics landscape of circRNA-mediated nucleolin ubiquitination and degradation in HCC metastasis.
  • Circ0006646 acts as a crucial regulator of HCC metastasis by stabilizing NCL.
  • Circ0006646 represents a novel and promising therapeutic target for hepatocellular carcinoma.
Keywords:
Circular RNAHepatocellular carcinomaNucleolinmulti‐omicsubiquitination

More Related Videos

Silencing of BRCA2 to Identify Novel BRCA2-regulated Biological Functions in Cultured Human Cells09:24

Silencing of BRCA2 to Identify Novel BRCA2-regulated Biological Functions in Cultured Human Cells

Published on: August 12, 2015

9.1K
In Silico Identification and Characterization of circRNAs During Host-Pathogen Interactions10:27

In Silico Identification and Characterization of circRNAs During Host-Pathogen Interactions

Published on: October 21, 2022

1.5K

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
Loss of Tumor Suppressor Gene Functions01:12

Loss of Tumor Suppressor Gene Functions

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.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
4.8K
Cancer-Critical Genes II: Tumor Suppressor Genes01:05

Cancer-Critical Genes II: Tumor Suppressor Genes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
7.4K
Cancer Stem Cells and Tumor Maintenance02:40

Cancer Stem Cells and Tumor Maintenance

Early diagnosis and treatment can often cure cancer. However, even with treatment, residual cells called cancer stem cells (CSC) might remain, often causing tumor recurrence. These cancer stem cells possess the potential for self-renewal and multi-lineage differentiation and are often responsible for the therapeutic resistance displayed in most cancers.
Cancer stem cells are thought to originate from tissue-specific normal stem cells or progenitor cells. The normal stem cells usually reside in...
4.9K
Adaptive Mechanisms in Cancer Cells02:53

Adaptive Mechanisms in Cancer Cells

Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
5.8K
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...
3.8K