Dataset Information

Genome-wide screening of circadian and non-circadian impact of Neat1 genetic deletion.

ABSTRACT: The functions of the long non-coding RNA, Nuclear enriched abundant transcript 1 (Neat1), are poorly understood. Neat1 is required for the formation of paraspeckles, but its respective paraspeckle-dependent or independent functions are unknown. Several studies including ours reported that Neat1 is involved in the regulation of circadian rhythms. We characterized the impact of Neat1 genetic deletion in a rat pituitary cell line. The mRNAs whose circadian expression pattern or expression level is regulated by Neat1 were identified after high-throughput RNA sequencing of the circadian transcriptome of wild-type cells compared to cells in which Neat1 was deleted by CRISPR/Cas9. The numerous RNAs affected by Neat1 deletion were found to be circadian or non-circadian, targets or non-targets of paraspeckles, and to be associated with many key biological processes showing that Neat1, in interaction with the circadian system or independently, could play crucial roles in key physiological functions through diverse mechanisms.

SUBMITTER: Jacq A

PROVIDER: S-EPMC8085668 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Genome-wide screening of circadian and non-circadian impact of Neat1 genetic deletion.

Jacq Audrey A Becquet Denis D Bello-Goutierrez Maria-Montserrat MM Boyer Bénédicte B Guillen Séverine S Franc Jean-Louis JL François-Bellan Anne-Marie AM

Computational and structural biotechnology journal 20210421

The functions of the long non-coding RNA, Nuclear enriched abundant transcript 1 (Neat1), are poorly understood. Neat1 is required for the formation of paraspeckles, but its respective paraspeckle-dependent or independent functions are unknown. Several studies including ours reported that Neat1 is involved in the regulation of circadian rhythms. We characterized the impact of Neat1 genetic deletion in a rat pituitary cell line. The mRNAs whose circadian expression pattern or expression level is ...[more]

PMID: 33995907

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Project description:BackgroundDysfunction of the circadian clock and single polymorphisms of some circadian genes have been linked to cancer susceptibility, although data are scarce and findings inconsistent. We aimed to investigate the association between circadian pathway genetic variation and risk of developing common cancers based on the findings of genome-wide association studies (GWASs).MethodsSingle nucleotide polymorphisms (SNPs) of 17 circadian genes reported by three GWAS meta-analyses dedicated to breast (Discovery, Biology, and Risk of Inherited Variants in Breast Cancer (DRIVE) Consortium; cases, n = 15,748; controls, n = 18,084), prostate (Elucidating Loci Involved in Prostate Cancer Susceptibility (ELLIPSE) Consortium; cases, n = 14,160; controls, n = 12,724) and lung carcinoma (Transdisciplinary Research In Cancer of the Lung (TRICL) Consortium; cases, n = 12,160; controls, n = 16,838) in patients of European ancestry were utilized to perform pathway analysis by means of the adaptive rank truncated product (ARTP) method. Data were also available for the following subgroups: estrogen receptor negative breast cancer, aggressive prostate cancer, squamous lung carcinoma and lung adenocarcinoma.ResultsWe found a highly significant statistical association between circadian pathway genetic variation and the risk of breast (pathway P value = 1.9 × 10-6; top gene RORA, gene P value = 0.0003), prostate (pathway P value = 4.1 × 10-6; top gene ARNTL, gene P value = 0.0002) and lung cancer (pathway P value = 6.9 × 10-7; top gene RORA, gene P value = 2.0 × 10-6), as well as all their subgroups. Out of 17 genes investigated, 15 were found to be significantly associated with the risk of cancer: four genes were shared by all three malignancies (ARNTL, CLOCK, RORA and RORB), two by breast and lung cancer (CRY1 and CRY2) and three by prostate and lung cancer (NPAS2, NR1D1 and PER3), whereas four genes were specific for lung cancer (ARNTL2, CSNK1E, NR1D2 and PER2) and two for breast cancer (PER1, RORC).ConclusionsOur findings, based on the largest series ever utilized for ARTP-based gene and pathway analysis, support the hypothesis that circadian pathway genetic variation is involved in cancer predisposition.

Dataset Information

Genome-wide screening of circadian and non-circadian impact of Neat1 genetic deletion.

Publications

Genome-wide screening of circadian and non-circadian impact of Neat1 genetic deletion.

Similar Datasets

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