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Transcriptome profiling in preadipocytes identifies long noncoding RNAs as Sam68 targets.

ABSTRACT: The KH-type RNA binding protein Sam68 is required for adipogenesis. We have previously shown that Sam68-deficient mice have a lean phenotype and are protected against dietary-induced obesity due to defects in mTOR and S6K1 alternative splicing. Herein we profiled the transcriptome of Sam68 wild type and deficient 3T3-L1 mouse preadipocytes. We identified 652 protein-coding genes and 9 ncRNAs that were significantly altered with the loss of Sam68. As expected, downregulated genes were significantly associated with GO terms linked to cell migration, motility, and fat cell differentiation, while upregulated genes were mostly associated with GO terms linked to neurogenesis. Of the lncRNAs, we identified Hotair, Mir155hg, as well as two new lncRNAs (SR-lncRNA-1 and SR-lncRNA-2) that were regulated by Sam68, and contained consensus Sam68 binding sites. RNA stability assays showed that Sam68-deficiency decreased the half-life of Hotair, and increased the half-lives of Mir155hg and SR-lncRNA-2, while the stability of SR-lncRNA-1 was unaffected. Depletion of Hotair and SR-lncRNA-1 in wild type 3T3-L1 cells led to defects in adipogenesis, whereas depletion of SR-lncRNA-2 in Sam68-deficient 3T3-L1 cells partially rescued the adipogenesis defect observed in these cells. Collectively, our findings define a new role for Sam68 as a regulator of lncRNAs during adipogenic differentiation.

SUBMITTER: Li N

PROVIDER: S-EPMC5669865 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Transcriptome profiling in preadipocytes identifies long noncoding RNAs as Sam68 targets.

Li Naomi N Hébert Steven S Song Jingwen J Kleinman Claudia L CL Richard Stéphane S

Oncotarget 20170511 47

The KH-type RNA binding protein Sam68 is required for adipogenesis. We have previously shown that Sam68-deficient mice have a lean phenotype and are protected against dietary-induced obesity due to defects in mTOR and S6K1 alternative splicing. Herein we profiled the transcriptome of Sam68 wild type and deficient 3T3-L1 mouse preadipocytes. We identified 652 protein-coding genes and 9 ncRNAs that were significantly altered with the loss of Sam68. As expected, downregulated genes were significant ...[more]

PMID: 29137239

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Project description:BackgroundPaclitaxel is a widely prescribed chemotherapy drug for treating solid tumors. However, paclitaxel-induced peripheral neuropathy (PIPN) is a common adverse effect during paclitaxel treatment, which results in sensory abnormalities and neuropathic pain among patients. Unfortunately, the mechanisms underlying PIPN still remain poorly understood. Long noncoding RNAs (lncRNAs) are novel and promising targets for chronic pain treatment, but their involvement in PIPN still remains unexplored.MethodsWe established a rat PIPN model by repetitive paclitaxel application. Immunostaining, RNA sequencing (RNA-Seq) and bioinformatics analysis were performed to study glia cell activation and explore lncRNA/mRNA expression profiles in spinal cord dorsal horn (SCDH) of PIPN model rats. qPCR and protein assay were used for further validation.ResultsPIPN model rats developed long-lasting mechanical and thermal pain hypersensitivities in hind paws, accompanied with astrocyte and microglia activation in SCDH. RNA-Seq identified a total of 814 differentially expressed mRNAs (DEmRNA) (including 467 upregulated and 347 downregulated) and 412 DElncRNAs (including 145 upregulated and 267 downregulated) in SCDH of PIPN model rats vs. control rats. Functional analysis of DEmRNAs and DElncRNAs identified that the most significantly enriched pathways include immune/inflammatory responses and neurotrophin signaling pathways, which are all important mechanisms mediating neuroinflammation, central sensitization, and chronic pain. We further compared our dataset with other published datasets of neuropathic pain and identified a core set of immune response-related genes extensively involved in PIPN and other neuropathic pain conditions. Lastly, a competing RNA network analysis of DElncRNAs and DEmRNAs was performed to identify potential regulatory networks of lncRNAs on mRNA through miRNA sponging.ConclusionsOur study provided the transcriptome profiling of DElncRNAs and DEmRNAs and uncovered immune and inflammatory responses were predominant biological events in SCDH of the rat PIPN model. Thus, our study may help to identify promising genes or signaling pathways for PIPN therapeutics.

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Transcriptome profiling in preadipocytes identifies long noncoding RNAs as Sam68 targets.

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Transcriptome profiling in preadipocytes identifies long noncoding RNAs as Sam68 targets.

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