Dataset Information

Human lung cancer cells-MS for SNHG3 c.1746A>I editing

ABSTRACT: Adenosine-to-inosine (A-to-I) RNA editing is a critical post-transcriptional modification that enhances tumor genome diversity and contributes to cancer progression. In non-small cell lung cancer (NSCLC), while specific A-to-I editing events have been identified, their functional mechanisms and clinical relevance remain poorly understood. Here, through whole-transcriptome analysis of NSCLC specimens, we discovered a hyper-editing event at position c.1746 in the long non-coding RNA SNHG3 (c.1746A>I), which correlates with advanced metastatic stages and reduced patient survival. Functional studies demonstrated that edited SNHG3 (SNHG3ED) exhibits significantly greater pro-metastatic activity compared to its wild-type counterpart (SNHG3WT). Mechanistically, SNHG3ED shows enhanced binding affinity for the chromatin remodeler SSRP1, triggering SSRP1-mediated replication origin assembly and subsequent upregulation of fatty acid metabolism and ferroptosis-related genes. This molecular rewiring promotes fatty acid oxidation, confers resistance to ferroptosis, and importantly, drives docetaxel (DTX) chemoresistance. In DTX-resistant NSCLC cell lines, patient-derived organoids and Nude mouse xenograft tumor model, antisense oligonucleotide-based targeting of SNHG3ED effectively restored DTX sensitivity and suppressed tumor growth. Our findings demonstrate that SNHG3 c.1746A>I editing serves both as a novel prognostic biomarker for NSCLC and as a mechanistically defined therapeutic target to overcome DTX resistance, which offers a potential therapeutic target to improve DTX efficacy.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell, Cell Culture

DISEASE(S): Lung Cancer

SUBMITTER: Lei Yang

LAB HEAD: Lei Yang

PROVIDER: PXD067139 | Pride | 2025-09-15

REPOSITORIES: Pride

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Publications

A-to-I edited SNHG3 promotes non-small cell lung cancer metastasis by promoting fatty acid oxidation and resisting ferroptosis.

Chen Shizhen S Zhuo Amei A Tang Renyu R Su Siming S Wen Binbin B Wei Wujun W Xie Jianjiang J Yu Ziqi Z Rao Boqi B Lu Jiachun J Deng Yibin Y Zhang Zhili Z Yang Lei L

Communications biology 20250902 1

Adenosine-to-inosine (A-to-I) RNA editing is a critical post-transcriptional modification that enhances tumor genome diversity and contributes to cancer progression. In non-small cell lung cancer (NSCLC), while specific A-to-I editing events have been identified, their functional mechanisms and clinical relevance remain poorly understood. Here, through whole-transcriptome analysis of NSCLC specimens, we discovered a hyper-editing event at position c.1746 in the long non-coding RNA SNHG3 (c.1746 ...[more]

PMID: 40897790

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