LncRNA CALML3-AS1 modulated by m6A modification induces BTNL9 methylation to drive non-small-cell lung cancer progression

Zhang, Heng; Wang, Shao-Qiang; Zhu, Jie-Bo; Wang, Li-Na; Lin, Hang; Li, Lin-Feng; Cheng, Yuan-Da; Duan, Chao-Jun; Zhang, Chun-Fang

doi:10.1038/s41417-023-00670-7

Cited by 9 publications

(1 citation statement)

References 37 publications

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“…To evaluate the Understanding the molecular mechanism of action of lncRNAs can help identify molecular markers for the early diagnosis and clinical treatment of lung cancer. 44,45 In this study, we observed that lncRNA DARS-AS1 is upregulated in NSCLC cell lines and tissues. Moreover, DARS-AS1 knockdown inhibited the proliferation, migration and invasion of NSCLC cells, and promoted NSCLC cells apoptosis.…”

Section: Dars-as1 Knockdown Inhibits Tumor Growth In Nude Micementioning

confidence: 58%

Silencing lncRNA‐DARS‐AS1 suppresses nonsmall cell lung cancer progression by stimulating miR‐302a‐3p to inhibit ACAT1 expression

Li,

Sun

et al. 2024

Molecular Carcinogenesis

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Long noncoding RNAs (LncRNAs) have been gaining attention as potential therapeutic targets for lung cancer. In this study, we investigated the expression and biological behavior of lncRNA DARS‐AS1, its predicted interacting partner miR‐302a‐3p, and ACAT1 in nonsmall cell lung cancer (NSCLC). The transcript level of DARS‐AS1, miR‐302a‐3p, and ACAT1 was analyzed using qRT‐PCR. Endogenous expression of ACAT1 and the expression of—and changes in—AKT/ERK pathway‐related proteins were determined using western blotting. MTS, Transwell, and apoptosis experiments were used to investigate the behavior of cells. The subcellular localization of DARS‐AS1 was verified using FISH, and its binding site was verified using dual‐luciferase reporter experiments. The binding of DARS‐AS1 to miR‐302a‐3p was verified using RNA co‐immunoprecipitation. In vivo experiments were performed using a xenograft model to determine the effect of DARS‐AS1 knockout on ACAT1 and NSCLC. lncRNA DARS‐AS1 was upregulated in NSCLC cell lines and tissues and the expression of lncRNA DARS‐AS1 was negatively correlated with survival of patients with NSCLC. Knockdown of DARS‐AS1 inhibited the malignant behaviors of NSCLC via upregulating miR‐302a‐3p. miR‐302a‐3p induced suppression of malignancy through regulating oncogene ACAT1. This study demonstrates that the DARS‐AS1‐miR‐302a‐3p‐ACAT1 pathway plays a key role in NSCLC.

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Section: Dars-as1 Knockdown Inhibits Tumor Growth In Nude Micementioning

confidence: 58%

Silencing lncRNA‐DARS‐AS1 suppresses nonsmall cell lung cancer progression by stimulating miR‐302a‐3p to inhibit ACAT1 expression

Li,

Sun

et al. 2024

Molecular Carcinogenesis

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Cis‐Regulation of an m⁶A Eraser by an Insertion Variant Associated with Survival of Patients With Non‐Small Cell Lung Carcinoma

Cheng,

Hu,

Wang

et al. 2024

Advanced Science

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N6‐methyladenosine (m6A) serves as one of the crucial RNA modifications for genes involved in cancer progression. Here, 7273 expression quantitative trait loci potentially regulating 30 m6A pathway genes are identified from the GTEx database, with 69 single nucleotide polymorphisms significantly associated with survival of non‐small cell lung carcinoma (NSCLC) patients (n = 1523) from the ongoing genome‐wide association study after false positive probability tests. Notably, the rs151198415 locus, situated in a potential enhancer region, demonstrated a prolonged survival effect with the C>CCACG insertion, which is validated in an independent prospective cohort (n = 237), yielding a pooled hazard ratio of 0.72 (p = 0.007). Mechanistically, the rs151198415 C>CCACG insertion engaged in long‐range interaction with the promoter of m6A eraser ALKBH5, promoting ALKBH5 transcription by the creation of an EGR1 binding site. Then, ALKBH5 upregulated FBXL5 expression by m6A demethylation, which is dependent on the ALKBH5 H204 amino acid site and specific m6A sites on FBXL5 mRNA. Finally, the ALKBH5‐FBXL5 axis reduces intracellular reactive oxygen species levels, leading to PI3K/AKT and NF‐kB pathway inhibition and consequently suppresses NSCLC proliferation and metastasis in vitro and in vivo. Triggered by an insertion variant, this remote cis‐regulation of m6A eraser and the downstream molecular events modulate the survival of NSCLC patients.

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LncRNA HOXB3OS improves high glucose-mediated podocyte damage and progression of diabetic kidney disease through enhancing SIRT1 mRNA stability

Wang,

Pang,

et al. 2025

Biomedicine & Pharmacotherapy

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LncRNA CALML3-AS1 modulated by m6A modification induces BTNL9 methylation to drive non-small-cell lung cancer progression

Cited by 9 publications

References 37 publications

Silencing lncRNA‐DARS‐AS1 suppresses nonsmall cell lung cancer progression by stimulating miR‐302a‐3p to inhibit ACAT1 expression

Silencing lncRNA‐DARS‐AS1 suppresses nonsmall cell lung cancer progression by stimulating miR‐302a‐3p to inhibit ACAT1 expression

Cis‐Regulation of an m⁶A Eraser by an Insertion Variant Associated with Survival of Patients With Non‐Small Cell Lung Carcinoma

LncRNA HOXB3OS improves high glucose-mediated podocyte damage and progression of diabetic kidney disease through enhancing SIRT1 mRNA stability

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LncRNA CALML3-AS1 modulated by m6A modification induces BTNL9 methylation to drive non-small-cell lung cancer progression

Cited by 9 publications

References 37 publications

Silencing lncRNA‐DARS‐AS1 suppresses nonsmall cell lung cancer progression by stimulating miR‐302a‐3p to inhibit ACAT1 expression

Silencing lncRNA‐DARS‐AS1 suppresses nonsmall cell lung cancer progression by stimulating miR‐302a‐3p to inhibit ACAT1 expression

Cis‐Regulation of an m6A Eraser by an Insertion Variant Associated with Survival of Patients With Non‐Small Cell Lung Carcinoma

LncRNA HOXB3OS improves high glucose-mediated podocyte damage and progression of diabetic kidney disease through enhancing SIRT1 mRNA stability

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Cis‐Regulation of an m⁶A Eraser by an Insertion Variant Associated with Survival of Patients With Non‐Small Cell Lung Carcinoma