HOTAIR Promotes Spiral Ganglion Neuron Proliferation via miR-211-5p/EYA3 Regulation

Area of Science:

• Neuroscience
• Molecular Biology
• Genetics

Background:

• Sensorineural hearing loss (SNHL) is a significant cause of disability, primarily due to the degeneration of spiral ganglion neurons (SGNs).
• Long non-coding RNAs (lncRNAs) have been implicated in SGN function, but their specific roles in SGN damage and repair remain largely unknown.

Purpose of the Study:

• To investigate the role of the lncRNA HOTAIR in the survival and proliferation of SGNs.
• To elucidate the molecular mechanisms by which HOTAIR influences SGNs, including its interactions with microRNAs and target genes.

Main Methods:

• Localization of lncRNA-HOTAIR in SGNs using fluorescence in situ hybridization (FISH) and nuclear-cytoplasmic separation (NCS).
• Manipulation of HOTAIR levels in primary mouse SGNs (sh-HOTAIR SGNs) to assess its effects.
• Analysis of gene and protein expression using qRT-PCR and Western blot.
• Assessment of SGN proliferation and apoptosis via CCK-8 and flow cytometry.
• Investigation of molecular interactions using RNA immunoprecipitation (RIP) and dual-luciferase assays.

Main Results:

• HOTAIR is predominantly localized in the cytoplasm of SGNs.
• Downregulation of HOTAIR significantly increased SGN apoptosis by approximately 30%.
• HOTAIR competitively binds to miR-211-5p, thereby promoting SGN proliferation and inhibiting apoptosis.
• miR-211-5p directly targets EYA3, suppressing SGN proliferation and increasing apoptosis, an effect reversed by EYA3 overexpression.

Conclusions:

• HOTAIR plays a crucial role in promoting SGN proliferation and survival.
• The HOTAIR/miR-211-5p/EYA3 axis is a key regulatory pathway in SGNs.
• HOTAIR represents a promising therapeutic target for treating sensorineural hearing loss.