Related Experiment Video

Updated: May 26, 2025

Trans-Tympanic Drug Delivery for the Treatment of Ototoxicity
09:52

Trans-Tympanic Drug Delivery for the Treatment of Ototoxicity

Published on: March 16, 2018

9.3K

STM2457 decreases m6A methylation to reduce cisplatin-induced ototoxicity via MAPK signaling

Jiahao Liao1, Xingxing Wu1, Qingdong Zeng2

  • 1Department of Otolaryngology, Shenzhen Institute of Translational Medicine, Shenzhen Key Laboratory of Nanozymes and Translational Cancer Research, Medical Innovation Technology Transformation Center, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen 518035, China; School of Pharmacy, Shenzhen University Medical School, Shenzhen University, Shenzhen, Guangdong 518055, China.

Biochemical Pharmacology
|February 21, 2025
PubMed

Insights

Reducing RNA methylation with STM2457 protects against cisplatin-induced ototoxicity and hair cell loss. This study reveals a mechanism involving the Mitogen-Activated Protein Kinases pathway, offering a potential therapeutic strategy for preventing hearing loss.

Area of Science:

  • Ototoxicity research
  • RNA methylation
  • Cancer therapeutics

Background:

  • Cisplatin chemotherapy can cause irreversible hearing loss (ototoxicity).
  • N6-methyladenosine (m6A) methylation is a key RNA modification.
  • Investigating m6A's role in cisplatin-induced ototoxicity is crucial for developing protective strategies.

Purpose of the Study:

  • To investigate the effect of the METTL3 inhibitor STM2457 on cisplatin-induced ototoxicity using in vitro cochlear explants.
  • To explore the potential of reducing RNA m6A methylation as a protective measure against cisplatin-induced hearing loss.

Main Methods:

  • Utilized in vitro cochlear explants as a model system.
  • Administered STM2457 pretreatment followed by cisplatin exposure.
  • Assessed reactive oxygen species (ROS) accumulation, hair cell (HC) loss, apoptosis (TUNEL labeling), and protein expression (BAX, BCL-XL).
  • Performed transcriptomic analysis to identify involved signaling pathways.

Main Results:

  • STM2457 pretreatment significantly reduced ROS accumulation and hair cell loss.
  • Apoptosis was significantly decreased, indicated by reduced TUNEL labeling and altered BAX/BCL-XL ratios.
  • Transcriptomic analysis revealed enrichment of the Mitogen-Activated Protein Kinases (MAPK) signaling pathway.
  • MAPK pathway activation counteracted the protective effects of STM2457 in cisplatin-treated HCs.

Conclusions:

  • Reducing RNA m6A methylation via STM2457 protects against cisplatin-induced ototoxicity and hair cell death.
  • The protective mechanism involves mitigating ROS accumulation and apoptosis.
  • The MAPK pathway plays a critical role in modulating STM2457's efficacy, highlighting a potential therapeutic target.
Keywords:
CisplatinMAPKOtotoxicitySTM2457m6A

More Related Videos

Dissection of Adult Mouse Utricle and Adenovirus-mediated Supporting-cell Infection11:13

Dissection of Adult Mouse Utricle and Adenovirus-mediated Supporting-cell Infection

Published on: March 28, 2012

23.7K
The Mouse Round-window Approach for Ototoxic Agent Delivery: A Rapid and Reliable Technique for Inducing Cochlear Cell Degeneration12:21

The Mouse Round-window Approach for Ototoxic Agent Delivery: A Rapid and Reliable Technique for Inducing Cochlear Cell Degeneration

Published on: November 26, 2015

17.3K

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...
21.1K
Electron Transport Chain: Complex I and II01:46

Electron Transport Chain: Complex I and II

The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
10.2K