Related Experiment Video

Updated: Sep 1, 2025

Author Spotlight: Genetic Profiling for Fluorouracil Response in Gastric Cancer
06:21

Author Spotlight: Genetic Profiling for Fluorouracil Response in Gastric Cancer

Published on: May 10, 2024

835

APAF1-Binding Long Noncoding RNA Promotes Tumor Growth and Multidrug Resistance in Gastric Cancer by Blocking

Qiang Wang1,2, Chen Chen3, Xiao Xu4

  • 1Department of Hepatobiliary Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, 210000, China.

Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|August 17, 2022
PubMed

Insights

A newly identified long noncoding RNA, ABL, promotes gastric cancer (GC) growth and drug resistance by inhibiting apoptosis. Targeting ABL with siRNA offers a promising therapeutic strategy for improving GC treatment outcomes.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Chemotherapy is the primary treatment for advanced gastric cancer (GC), but drug resistance and toxicity limit its efficacy.
  • Long noncoding RNAs (lncRNAs) are increasingly recognized for their roles in cancer progression, including GC.

Purpose of the Study:

  • To identify novel lncRNAs involved in GC pathogenesis and drug resistance.
  • To elucidate the molecular mechanisms underlying the function of a specific lncRNA, ABL, in GC.
  • To evaluate ABL as a potential prognostic biomarker and therapeutic target for GC.

Main Methods:

  • RNA screening to identify differentially expressed lncRNAs in GC tissues.
  • Functional studies using GC cell lines, xenograft, and organoid models to assess the role of ABL in apoptosis, survival, and drug resistance.
  • Molecular mechanism studies involving RNA-binding protein interactions, m6A modification analysis, and apoptosis pathway assays.
  • In vivo studies using liposomal siRNA to target ABL and assess its therapeutic potential in combination with chemotherapy.

Main Results:

  • ABL, an apoptotic protease-activating factor 1 (APAF1)-binding lncRNA, is significantly upregulated in GC tissues and serves as an independent prognostic factor.
  • ABL overexpression enhances GC cell survival, inhibits apoptosis, and promotes multidrug resistance.
  • ABL stabilizes itself through interaction with IGF2BP1 and METTL3-mediated m6A modification.
  • ABL impedes apoptosome formation by preventing cytochrome c binding to APAF1, thereby blocking caspase activation and promoting cell death resistance.
  • Targeting ABL with liposomal siRNA significantly improves GC cell sensitivity to chemotherapy.

Conclusions:

  • ABL is a key oncogenic lncRNA in gastric cancer, promoting tumor progression and chemoresistance.
  • ABL represents a potential prognostic biomarker for GC patients.
  • Targeting ABL offers a promising therapeutic strategy to overcome drug resistance and improve outcomes in gastric cancer treatment.
Keywords:
ABLIGF2BP1apoptosisapoptotic protease-activating factor 1 (APAF1)drug resistancegastric cancerm6A

More Related Videos

Automated Preparation of [68Ga]Ga-3BP-3940 on a Synthesis Module for PET Imaging of the Tumor Microenvironment10:33

Automated Preparation of [68Ga]Ga-3BP-3940 on a Synthesis Module for PET Imaging of the Tumor Microenvironment

Published on: April 25, 2025

348
Combined Use of Tail Vein Metastasis Assays and Real-Time In Vivo Imaging to Quantify Breast Cancer Metastatic Colonization and Burden in the Lungs10:32

Combined Use of Tail Vein Metastasis Assays and Real-Time In Vivo Imaging to Quantify Breast Cancer Metastatic Colonization and Burden in the Lungs

Published on: December 19, 2019

11.0K

Related Concept Videos

lncRNA - Long Non-coding RNAs02:39

lncRNA - Long Non-coding RNAs

In humans, more than 80% of the genome gets transcribed. However, only around 2% of the genome codes for proteins. The remaining part produces non-coding RNAs which includes ribosomal RNAs, transfer RNAs, telomerase RNAs, and regulatory RNAs, among other types. A large number of regulatory non-coding RNAs have been classified into two groups depending upon their length – small non-coding RNAs, such as microRNA, which are less than 200 nucleotides in length, and long non-coding RNA...
8.8K
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...
4.6K
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...
3.9K
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
6.7K
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...
6.2K
The Ras Gene02:38

The Ras Gene

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a...
6.4K