Long non-coding RNA MEG3 promotes cataractogenesis by upregulating TP53INP1 expression in age-related cataract

Area of Science:

• Ophthalmology
• Molecular Biology
• Genetics

Background:

• Age-related cataract (ARC) is a primary cause of vision loss in the elderly.
• Long non-coding RNAs (LncRNAs) are implicated as potential regulators of ARC.
• Maternally expressed gene 3 (MEG3) is known to affect apoptosis and proliferation in cancer cells, but its role in ARC is unexplored.

Purpose of the Study:

• To investigate the expression and function of MEG3 in age-related cataract (ARC).
• To elucidate the underlying molecular mechanisms by which MEG3 influences ARC progression.

Main Methods:

• Quantification of MEG3 expression in age-related cortical cataract (ARCC) tissues.
• Analysis of apoptosis-related proteins (caspase-3, Bax, Bcl-2) in lens capsules.
• In vitro experiments involving knockdown of MEG3 in lens epithelial cells (LECs) under oxidative stress (H2O2).
• Investigation of MEG3's interaction with miR-223 and its effect on TP53INP1 and P53 expression.
• Assessment of TP53INP1 knockdown effects on H2O2-induced lens turbidity.

Main Results:

• MEG3 expression was elevated in ARCC tissues and correlated with disease severity.
• Pro-apoptotic proteins increased while anti-apoptotic proteins decreased in ARCC lenses.
• MEG3 knockdown enhanced LEC viability and reduced apoptosis under oxidative stress.
• MEG3 acted as a miR-223 sponge, promoting TP53INP1 and P53 expression.
• TP53INP1 knockdown mitigated oxidative stress-induced lens opacity.

Conclusions:

• MEG3 promotes ARC progression by upregulating TP53INP1 via miR-223 suppression and P53 promotion.
• MEG3 plays a significant role in the pathogenesis of age-related cataract.
• These findings provide novel insights into the molecular mechanisms of ARC.