LncRNA MT1DP Aggravates Cadmium-Induced Oxidative Stress by Repressing the Function of Nrf2 and is Dependent on...

Area of Science:

• Molecular Biology
• Toxicology
• Cellular Signaling

Background:

• Cadmium (Cd) is a known hepatotoxin, but the precise cellular signaling pathways governing its toxicity remain unclear.
• The balance between cell survival and apoptosis in response to Cd exposure is poorly understood at the molecular level.
• Long non-coding RNA (lncRNA) MT1DP has been implicated in promoting Cd-induced cell death.

Purpose of the Study:

• To elucidate the molecular mechanisms by which lncRNA MT1DP influences cadmium toxicity.
• To define the role of transcription factor MTF1 in MT1DP induction.
• To investigate the interplay between MT1DP, miR-365, and nuclear factor erythroid 2-related factor 2 (Nrf2) in cadmium-induced oxidative stress.

Main Methods:

• Investigated the dependency of MT1DP induction on the transcription factor MTF1.
• Established miR-365 as a mediator between MT1DP and Nrf2.
• Proposed and validated a novel mechanism for MT1DP-mediated miR-365 stabilization.

Main Results:

• MT1DP induction under Cd stress is dependent on MTF1.
• MT1DP decreases Nrf2 levels by elevating miR-365, which directly binds to Nrf2's 3'UTR.
• A new mechanism shows MT1DP stabilizes miR-365 RNA, leading to reduced Nrf2-mediated cellular protection and increased oxidative stress.

Conclusions:

• lncRNA MT1DP plays a critical role in diminishing Nrf2-mediated cellular protection during Cd exposure.
• The interaction between MT1DP and miR-365 is crucial for modulating oxidative stress.
• This study expands the understanding of how inducible endogenous lncRNAs regulate oxidative stress responses.