LncRNA MALAT1 Targets METTL3 to Orchestrate INPP5B/LRIG2 Signaling and Promote Non‐Small Cell Lung Cancer Progression
- 1Hainan Pharmaceutical Research and Development Science Park Hainan Medical University Haikou People's Republic of China
- 2Department of Thoracic Surgery The Second Affiliated Hospital of Hainan Medical University Haikou People's Republic of China
Abstract
m6A modification regulates the functions of long non‐coding RNAs (lncRNAs) through diverse mechanisms. However, whether the lncRNA MALAT1 regulates the progression of non‐small cell lung cancer (NSCLC) through targeted regulation of METTL3 remains unclear, and the underlying molecular mechanisms have yet to be elucidated. This study aimed to investigate the role of MALAT1 in NSCLC progression by targeting and regulating METTL3. NCI‐H226 NSCLC cells were used as experimental models. RIP and FISH assays were performed to validate the physical interaction between MALAT1 and METTL3. Cells were co‐transfected with si‐MALAT1 and METTL3 overexpression constructs for rescue experiments. FISH was used to determine the subcellular localization of MALAT1. Apoptotic activity was quantified by flow cytometry, while cell proliferation was assessed using the EdU incorporation assay. The Transwell assay was performed to evaluate cell migration, and the EpiQuik m6A RNA Methylation Quantification Kit was used to detect cellular m6A methylation levels. Xenograft mouse models were established to evaluate in vivo tumor growth, and clinical NSCLC specimens were analyzed to investigate the clinical correlation among METTL3, INPP5B, and LRIG2. The experimental results showed that MALAT1 was predominantly localized in the nucleus and interacted with METTL3. Following si‐MALAT1 treatment, cell proliferation and migration were decreased, although no significant change was observed in colony formation ability. Furthermore, apoptosis was increased, accompanied by cell cycle arrest at the G0/G1 phase. After MALAT1 interference, transfection with a METTL3 overexpression vector reversed these malignant phenotypes, reduced apoptosis, induced S‐phase accumulation, and significantly downregulated the tumor suppressor gene INPP5B while upregulating the oncoprotein LRIG2. Consistently, in vivo xenograft assays demonstrated that MALAT1 knockdown suppressed tumor growth, which was rescued by METTL3 overexpression. Clinical sample analysis further supported the correlation among METTL3, INPP5B, and LRIG2 in NSCLC tissues. These findings substantiate the regulatory role of MALAT1‐mediated METTL3 modulation in NSCLC progression through the INPP5B/LRIG2 signaling axis.
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BibTeX
@article{tian2026lncrna,
title = {{LncRNA MALAT1 Targets METTL3 to Orchestrate INPP5B/LRIG2 Signaling and Promote Non‐Small Cell Lung Cancer Progression}},
author = {Shuhong Tian and Fayu Ling and Dunzhi Fu and Qiongyu Wang and Fan Li and Biao Li},
journal = {Chemical Biology \& Drug Design},
year = {2026},
month = oct,
doi = {10.1111/cbdd.70421},
url = {https://doi.org/10.1111/cbdd.70421},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - LncRNA MALAT1 Targets METTL3 to Orchestrate INPP5B/LRIG2 Signaling and Promote Non‐Small Cell Lung Cancer Progression
AU - Shuhong Tian
AU - Fayu Ling
AU - Dunzhi Fu
AU - Qiongyu Wang
AU - Fan Li
AU - Biao Li
PY - 2026
DA - 2026/10/26
JO - Chemical Biology & Drug Design
DO - 10.1111/cbdd.70421
UR - https://doi.org/10.1111/cbdd.70421
AB - m6A modification regulates the functions of long non‐coding RNAs (lncRNAs) through diverse mechanisms. However, whether the lncRNA MALAT1 regulates the progression of non‐small cell lung cancer (NSCLC) through targeted regulation of METTL3 remains unclear, and the underlying molecular mechanisms have yet to be elucidated. This study aimed to investigate the role of MALAT1 in NSCLC progression by targeting and regulating METTL3. NCI‐H226 NSCLC cells were used as experimental models. RIP and FISH assays were performed to validate the physical interaction between MALAT1 and METTL3. Cells were co‐transfected with si‐MALAT1 and METTL3 overexpression constructs for rescue experiments. FISH was used to determine the subcellular localization of MALAT1. Apoptotic activity was quantified by flow cytometry, while cell proliferation was assessed using the EdU incorporation assay. The Transwell assay was performed to evaluate cell migration, and the EpiQuik m6A RNA Methylation Quantification Kit was used to detect cellular m6A methylation levels. Xenograft mouse models were established to evaluate in vivo tumor growth, and clinical NSCLC specimens were analyzed to investigate the clinical correlation among METTL3, INPP5B, and LRIG2. The experimental results showed that MALAT1 was predominantly localized in the nucleus and interacted with METTL3. Following si‐MALAT1 treatment, cell proliferation and migration were decreased, although no significant change was observed in colony formation ability. Furthermore, apoptosis was increased, accompanied by cell cycle arrest at the G0/G1 phase. After MALAT1 interference, transfection with a METTL3 overexpression vector reversed these malignant phenotypes, reduced apoptosis, induced S‐phase accumulation, and significantly downregulated the tumor suppressor gene INPP5B while upregulating the oncoprotein LRIG2. Consistently, in vivo xenograft assays demonstrated that MALAT1 knockdown suppressed tumor growth, which was rescued by METTL3 overexpression. Clinical sample analysis further supported the correlation among METTL3, INPP5B, and LRIG2 in NSCLC tissues. These findings substantiate the regulatory role of MALAT1‐mediated METTL3 modulation in NSCLC progression through the INPP5B/LRIG2 signaling axis.
SN - 1747-0277
SN - 1747-0285
ER -