LncRNA TMEM99 Complexes with IGF2BP2 to Inhibit Autophagy in Lung Adenocarcinoma

Lung adenocarcinoma (LUAD), the most common type of lung cancer, has a poor prognosis. Long noncoding RNAs (lncRNAs) play a key role in LUAD progression, yet the biological role of lncRNA TMEM99 remains unexplored. In this study, its function in inhibiting autophagy in LUAD is explored. Using RNA sequencing and quantitative reverse transcription PCR (qRT-PCR), TMEM99 is found upregulated in LUAD tissues and cell lines, correlating with poor patient outcomes. In vivo and in vitro assays confirmed that TMEM99 promotes cell proliferation, migration, and invasion, and inhibits autophagy. Mechanistically, the 3' end of TMEM99 binds to the K‑homology domain 1 (KH1) and KH4 domains of far upstream element‑binding protein 3 (FUBP3), stabilizing its protein. The TMEM99-FUBP3 complex binds to p21 mRNA and recruits IGF2BP2 in an N⁶‑methyladenosine (m⁶A)-dependent manner, which enhances mRNA stability and translation efficiency. This study reveals that TMEM99 plays a crucial regulatory role in LUAD autophagy and presents a novel cytoplasmic regulatory mechanism contributing to LUAD progression.

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Publication Details

Journal
Advanced Science
Published
2025-07-24
DOI
https://doi.org/10.1002/advs.202507871
Primary Topic
Cancer-related molecular mechanisms research
Type
article
Field-Weighted Citation Impact
0.00

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article

LncRNA TMEM99 Complexes with IGF2BP2 to Inhibit Autophagy in Lung Adenocarcinoma

Dali Zheng, Yang Wo, Zhigang Wu, X. Chen et al.
Advanced Science
Cancer-related molecular mechanisms research
article

LncRNA TMEM99 Complexes with IGF2BP2 to Inhibit Autophagy in Lung Adenocarcinoma

Dali Zheng, Yang Wo, Zhigang Wu, X. Chen, Chongze Yuan, Pengcheng Liu, Qixuan Huang, Yunjian Pan, Yan Shang, Yue Zhao, Yihua Sun, Hui Hong, Yizhou Peng
article en

Abstract

Lung adenocarcinoma (LUAD), the most common type of lung cancer, has a poor prognosis. Long noncoding RNAs (lncRNAs) play a key role in LUAD progression, yet the biological role of lncRNA TMEM99 remains unexplored. In this study, its function in inhibiting autophagy in LUAD is explored. Using RNA sequencing and quantitative reverse transcription PCR (qRT-PCR), TMEM99 is found upregulated in LUAD tissues and cell lines, correlating with poor patient outcomes. In vivo and in vitro assays confirmed that TMEM99 promotes cell proliferation, migration, and invasion, and inhibits autophagy. Mechanistically, the 3' end of TMEM99 binds to the K‑homology domain 1 (KH1) and KH4 domains of far upstream element‑binding protein 3 (FUBP3), stabilizing its protein. The TMEM99-FUBP3 complex binds to p21 mRNA and recruits IGF2BP2 in an N⁶‑methyladenosine (m⁶A)-dependent manner, which enhances mRNA stability and translation efficiency. This study reveals that TMEM99 plays a crucial regulatory role in LUAD autophagy and presents a novel cytoplasmic regulatory mechanism contributing to LUAD progression.

Advanced ScienceVol. 12(33)
Kunming Medical University (CN), Fudan University Shanghai Cancer Center (CN), Shanghai Ninth People's Hospital (CN)
Beijing Xisike Clinical Oncology Research Foundation, Science and Technology Commission of Shanghai Municipality, National Science Fund for Distinguished Young Scholars
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Cancer-related molecular mechanisms research
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