Dataset Information

The DNA damage inducible lncRNA SCAT7 regulates genomic integrity and topoisomerase 1 turnover in lung adenocarcinoma.

ABSTRACT: Despite the rapid improvements in unveiling the importance of lncRNAs in all aspects of cancer biology, there is still a void in mechanistic understanding of their role in the DNA damage response. Here we explored the potential role of the oncogenic lncRNA SCAT7 (ELF3-AS1) in the maintenance of genome integrity. We show that SCAT7 is upregulated in response to DNA-damaging drugs like cisplatin and camptothecin, where SCAT7 expression is required to promote cell survival. SCAT7 silencing leads to decreased proliferation of cisplatin-resistant cells in vitro and in vivo through interfering with cell cycle checkpoints and DNA repair molecular pathways. SCAT7 regulates ATR signaling, promoting homologous recombination. Importantly, SCAT7 also takes part in proteasome-mediated topoisomerase I (TOP1) degradation, and its depletion causes an accumulation of TOP1-cc structures responsible for the high levels of intrinsic DNA damage. Thus, our data demonstrate that SCAT7 is an important constituent of the DNA damage response pathway and serves as a potential therapeutic target for hard-to-treat drug resistant cancers.

SUBMITTER: Statello L

PROVIDER: S-EPMC8209975 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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The DNA damage inducible lncRNA SCAT7 regulates genomic integrity and topoisomerase 1 turnover in lung adenocarcinoma.

Statello Luisa L Ali Mohamad M MM Reischl Silke S Mahale Sagar S Kosalai Subazini Thankaswamy ST Huarte Maite M Kanduri Chandrasekhar C

NAR cancer 20210201 1

Despite the rapid improvements in unveiling the importance of lncRNAs in all aspects of cancer biology, there is still a void in mechanistic understanding of their role in the DNA damage response. Here we explored the potential role of the oncogenic lncRNA SCAT7 (ELF3-AS1) in the maintenance of genome integrity. We show that SCAT7 is upregulated in response to DNA-damaging drugs like cisplatin and camptothecin, where SCAT7 expression is required to promote cell survival. SCAT7 silencing leads to ...[more]

PMID: 34316698

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Project description:Background: Lung adenocarcinoma (LUAD) is a highly heterogeneous tumor with substantial somatic mutations and genome instability, which are emerging hallmarks of cancer. Long non-coding RNAs (lncRNAs) are promising cancer biomarkers that are reportedly involved in genomic instability. However, the identification of genome instability-related lncRNAs (GInLncRNAs) and their clinical significance has not been investigated in LUAD. Methods: We determined GInLncRNAs by combining somatic mutation and transcriptome data of 457 patients with LUAD and probed their potential function using co-expression network and Gene Ontology (GO) enrichment analyses. We then filtered GInLncRNAs by Cox regression and LASSO regression to construct a genome instability-related lncRNA signature (GInLncSig). We subsequently evaluated GInLncSig using correlation analyses with mutations, external validation, model comparisons, independent prognostic significance analyses, and clinical stratification analyses. Finally, we established a nomogram for prognosis prediction in patients with LUAD and validated it in the testing set and the entire TCGA dataset. Results: We identified 161 GInLncRNAs, of which seven were screened to develop a prognostic GInLncSig model (LINC01133, LINC01116, LINC01671, FAM83A-AS1, PLAC4, MIR223HG, and AL590226.1). GInLncSig independently predicted the overall survival of patients with LUAD and displayed an improved performance compared to other similar signatures. Furthermore, GInLncSig was related to somatic mutation patterns, suggesting its ability to reflect genome instability in LUAD. Finally, a nomogram comprising the GInLncSig and tumor stage exhibited improved robustness and clinical practicability for predicting patient prognosis. Conclusion: Our study identified a signature for prognostic prediction in LUAD comprising seven lncRNAs associated with genome instability, which may provide a useful indicator for clinical stratification management and treatment decisions for patients with LUAD.

Dataset Information

The DNA damage inducible lncRNA SCAT7 regulates genomic integrity and topoisomerase 1 turnover in lung adenocarcinoma.

Publications

The DNA damage inducible lncRNA SCAT7 regulates genomic integrity and topoisomerase 1 turnover in lung adenocarcinoma.

Similar Datasets

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