Related Experiment Video

Updated: May 3, 2026

Author Spotlight: Unveiling Transmembrane Protein Family-Related Markers in Gastric Cancer and Implications for Targeted Therapies
07:47

Author Spotlight: Unveiling Transmembrane Protein Family-Related Markers in Gastric Cancer and Implications for Targeted Therapies

Published on: September 15, 2023

2.2K

NSUN5-CBX8 m5C axis promotes gastric tumorigenesis by activating JAK-STAT3 signaling

Jingyi Yin1, Lingmeng Li1, Yinan Niu1

  • 1Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China.

Cellular Signalling
|May 1, 2026
PubMed

Insights

NSUN5 RNA methylation drives gastric cancer (GC) by stabilizing CBX8 mRNA, activating JAK-STAT3 signaling. Inhibiting CBX8 with SW2-110A offers a potential therapeutic strategy for GC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Epigenetics

Background:

  • Dysregulated RNA methylation is increasingly linked to cancer development.
  • NSUN5 is frequently altered in gastric cancer (GC), but its role is unclear.

Purpose of the Study:

  • To elucidate the functional and mechanistic role of NSUN5 in gastric tumorigenesis.
  • To identify potential therapeutic targets for GC.

Main Methods:

  • Utilized a Trp53; Kras; Villin-Cre mouse model for gastric tumorigenesis.
  • Investigated NSUN5's catalytic activity and its effect on CBX8 mRNA stability.
  • Analyzed the impact of NSUN5 on the PRC1 complex, JAK-STAT3 pathway, and SOCS2 expression.
  • Tested the efficacy of a CBX8 inhibitor (SW2-110A) in a preclinical setting.

Main Results:

  • Nsun5 gene depletion significantly suppressed gastric tumor formation in mice.
  • Wild-type NSUN5, but not a catalytically inactive mutant, rescued tumor formation.
  • NSUN5 stabilizes CBX8 mRNA, increasing CBX8 protein levels and activating the JAK-STAT3 pathway via SOCS2 inhibition.
  • The CBX8 inhibitor SW2-110A effectively antagonized NSUN5-driven GC cell tumorigenesis.

Conclusions:

  • NSUN5 drives gastric tumorigenesis by regulating CBX8 protein levels and activating the JAK-STAT3 signaling pathway.
  • Targeting NSUN5 or its downstream effector CBX8 presents a promising therapeutic strategy for gastric cancer.
Keywords:
CBX8Gastric cancerJAK–STAT3NSUN5m(5)C methylation

More Related Videos

An Immunofluorescent Method for Characterization of Barrett’s Esophagus Cells08:54

An Immunofluorescent Method for Characterization of Barrett’s Esophagus Cells

Published on: July 20, 2014

13.1K
Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter11:32

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter

Published on: March 27, 2020

6.5K

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...
3.6K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

1.5K
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
10.2K
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...
4.0K
Induced Pluripotent Stem Cells01:06

Induced Pluripotent Stem Cells

Stem cells are undifferentiated cells that divide and produce different cell types. Ordinarily, cells that have differentiated into a specific cell type are terminally differentiated; however, scientists have found a way to reprogram these mature cells so that they dedifferentiate and return to an unspecialized, proliferative state. These cells are pluripotent like embryonic stem cells—able to produce all cell types—and are called induced pluripotent stem cells (iPSCs).
Somatic...
4.8K
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...
4.9K