WCLC 2025 - Posters & ePosters-P2.02.19 SIN3A/MIR22HG/Beclin1 Axis Regulates Both Autophagy and Ferroptosis in Lung Adenocarcinoma

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This study investigates the role of the MIR22HG/SIN3A/Beclin1 molecular axis in regulating autophagy and ferroptosis, two forms of regulated cell death, in lung adenocarcinoma (LUAD). LUAD, a major non-small cell lung cancer subtype, has a poor prognosis with a 5-year survival rate under 20%. The long non-coding RNA MIR22HG, previously identified as downregulated in LUAD and associated with better patient survival, was found to activate Beclin1-dependent autophagy and promote ferroptosis. Notably, ferroptosis counterbalances autophagy's potential pro-tumor growth effects. Beclin1 is essential for both pathways but does not bind directly to MIR22HG.<br /><br />SIN3A, a transcriptional co-repressor, was identified as a direct MIR22HG-binding protein that suppresses MIR22HG expression. Silencing SIN3A elevates MIR22HG levels, thereby reactivating autophagy and ferroptosis, leading to reduced LUAD cell proliferation, migration, and invasion. These findings were supported by cell culture studies using LUAD cell lines (H1299, H1975), RNA interference, overexpression, and assays measuring autophagy markers (LC3B, Beclin1, p62) and ferroptosis indicators (ROS, GPX4, SLC7A11). In vivo xenograft models confirmed that MIR22HG overexpression suppressed tumor growth. Dual knockdown experiments further validated the regulatory interplay between SIN3A and MIR22HG.<br /><br />Overall, MIR22HG acts as a tumor suppressor by controlling autophagy and ferroptosis, while SIN3A acts as its upstream negative regulator. This axis offers promising therapeutic targets and biomarkers for LUAD, suggesting that relieving SIN3A-mediated repression could enhance MIR22HG activity and suppress tumor progression. The study provides new insights into LUAD biology and potential dual-target treatment strategies involving these pathways.

Asset Subtitle

Xiaobi Huang

Meta Tag

Speaker Xiaobi Huang

Topic Tumor Biology – Preclinical Biology

Keywords

MIR22HG

SIN3A

Beclin1

autophagy

ferroptosis

lung adenocarcinoma

non-small cell lung cancer

tumor suppressor

cell proliferation

therapeutic targets