SNHG17 Interacts with LRPPRC to Stabilize c-Myc and Promote G1/S Transition and Cell Proliferation
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA700980 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR13666800_1.fastq.gz | Fastqsanger.gz | |||
| SRR13666800_2.fastq.gz | Fastqsanger.gz | |||
| SRR13666801_1.fastq.gz | Fastqsanger.gz | |||
| SRR13666801_2.fastq.gz | Fastqsanger.gz | |||
| SRR13666802_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 12 |
Similar Datasets
Project description:Long non-coding RNAs (lncRNAs) emerge as new regulators of various cell activities. The G1 to S phase (G1/S) transition is the key step that drives cell to the division cycle, and its dysregulation contributes to unrestrained cell proliferation and consequent tumor development.In this study, we examined lncRNA expression profiles during cell cycle using serum starvation-stimulation model in human skin fibroblasts (SFs) and identified that lncRNA SnoRNA Host Gene 17 (SNHG17) was elevated at the early G1 phase and in hepatocellular carcinoma (HCC) tissues. Both gain- and loss-of function studies disclosed that SNHG17 increased c-Myc protein level, accelerated G1/S transition and cell proliferation, and consequently promoted tumor growth. Up-regulation of SNHG17 was correlated with high c-Myc level in human HCC. Mechanistically, the 1-150-nt of SNHG17 physically interacted with the 1035-1369-aa of leucine rich pentatricopeptide repeat containing (LRPPRC) protein, and disrupting this interaction abrogated the promoting role of SNHG17 in c-Myc up-regulation, G1/S transition and cell proliferation. And the proliferation-stimulatory effect of SNHG17 was abrogated by silencing c-Myc or LRPPRC. Furthermore, silencing SNHG17 or LRPPRC increased the ubiquitylated c-Myc level and reduced c-Myc stability, suggesting that SNHG17 may inhibit c-Myc ubiquitination and thus enhance c-Myc level and facilitate proliferation by interacting with LRPPRC. Our findings identify a novel SNHG17-LRPPRC-c-Myc regulatory axis and elucidate its roles in G1/S transition and tumor growth, which provide potential targets for cancer therapy.
2021-02-10 | GSE166448 | GEO
Project description:Oncogenic c-Myc is a master regulator of G1/S transition. Long non-coding RNAs (lncRNAs) emerge as new regulators of various cell activities. Here, we found that lncRNA SnoRNA Host Gene 17 (SNHG17) was elevated at the early G1-phase of cell cycle. Both gain- and loss-of function studies disclosed that SNHG17 increased c-Myc protein level, accelerated G1/S transition and cell proliferation, and consequently promoted tumor cell growth in vitro and in vivo. Mechanistically, the 1-150-nt of SNHG17 physically interacted with the 1035-1369-aa of leucine rich pentatricopeptide repeat containing (LRPPRC) protein, and disrupting this interaction abrogated the promoting role of SNHG17 in c-Myc expression, G1/S transition, and cell proliferation. The effect of SNHG17 in stimulating cell proliferation was attenuated by silencing c-Myc or LRPPRC. Furthermore, silencing SNHG17 or LRPPRC increased the level of ubiquitylated c-Myc and reduced the stability of c-Myc protein. Analysis of human hepatocellular carcinoma (HCC) tissues revealed that SNHG17, LRPPRC, and c-Myc were significantly upregulated in HCC, and they showed a positive correlation with each other. High level of SNHG17 or LRPPRC was associated with worse survival of HCC patients. These data suggest that SNHG17 may inhibit c-Myc ubiquitination and thus enhance c-Myc level and facilitate proliferation by interacting with LRPPRC. Our findings identify a novel SNHG17-LRPPRC-c-Myc regulatory axis and elucidate its roles in G1/S transition and tumor growth, which may provide potential targets for cancer therapy.
| S-EPMC8528917 | biostudies-literature
Project description:To investigate the role of LRPPRC and mutant LRPPRC on the stability of the mitochondrially encoded mRNA transcripts.
2023-12-22 | GSE221586 | GEO
Project description:Rapid advances in genotyping and sequencing technology have dramatically accelerated the discovery of genes underlying human disease. Elucidating the function of such genes and understanding their role in pathogenesis, however, remains challenging. Here, we introduce a genomic strategy to functionally characterize such genes, and apply it to LRPPRC (leucine-rich PPR-motif containing), a poorly studied gene that is mutated in Leigh Syndrome, French Canadian type (LSFC). We utilize RNAi to engineer an allelic series of cellular models in which LRPPRC has been stably silenced to different levels of knockdown efficiency. Using expression profiling, we discovered a specific role for LRPPRC in the expression of all mitochondrial DNA (mtDNA)-encoded mRNAs, but not the rRNAs, without affecting nuclear genes encoding mitochondrial proteins. We designed seven shRNAs targeting the LRPPRC cDNA sequence to silence its expression in MCH58 immortalized human fibroblasts. The LRPPRC expression level in these cells ranged from 9% to 100%. We demonstrated that knockdown cells carried stable silencing of the target gene and associated biochemical phenotypes. Our goal was to engineer stable knockdown cells which recapitulate the LSFC disease phenotype and subject them to expression profiling using Affymetric microarrays to identify genesets and biochemical pathways that are altered.
2010-03-23 | E-GEOD-20847 | biostudies-arrayexpress
Project description:Differential gene expression among HEK293T WT, LRPPRC-KO, LRPPRC-KO + WT, and LRPPRC-KO + Leigh Syndrome French Canadian type LRPPRC
| PRJNA915041 | ENA
Project description:To map target transcripts bound with LRPPRC.
2023-05-10 | GSE204923 | GEO
Project description:Targeted inhibition of mitochondrial oxidative phosphorylation (OXPHOS) complex generation is an emerging and promising cancer treatment strategy, but limited targets and specific inhibitors have been reported. Leucine-rich pentatricopeptide repeat-containing protein (LRPPRC) is an atypical RNA-binding protein that regulates the stability of all 13 mitochondrial DNA-encoded mRNA (mt-mRNA) and thus participates in the synthesis of the OXPHOS complex. LRPPRC is also a prospective therapeutic target for lung adenocarcinoma, serving as a promising target for OXPHOS inhibition. In this study, we identified Demethylzeylasteral (T-96), a small molecule extracted from the Chinese herb Tripterygium wilfordii Hook. f., as a novel inhibitor of LRPPRC. T-96 directly bound to the RNA-binding domain of LRPPRC, inhibiting its interaction with mt-mRNA. This led to instability in both mt-mRNA and LRPPRC protein. Treatment with T-96 significantly reduced the mRNA and protein levels of the OXPHOS complex. As a consequence of LRPPRC inhibition, T-96 treatment induced a defect in the synthesis of the OXPHOS complex, inhibiting mitochondrial aerobic respiration and ATP synthesis. Moreover, T-96 exhibited potent antitumor activity for lung adenocarcinoma in vitro and in vivo, and the antitumor effect of T-96 was dependent on LRPPRC expression. In conclusion, this study not only identified the first traditional Chinese medicine monomer inhibitor against OXPHOS complex biosynthesis as well as a novel target of Demethylzeylasteral, but also shed light on the unique antitumor mechanism of bioactive compounds derived from traditional Chinese medicine.
2024-10-09 | GSE279114 | GEO
Project description:Rapid advances in genotyping and sequencing technology have dramatically accelerated the discovery of genes underlying human disease. Elucidating the function of such genes and understanding their role in pathogenesis, however, remains challenging. Here, we introduce a genomic strategy to functionally characterize such genes, and apply it to LRPPRC (leucine-rich PPR-motif containing), a poorly studied gene that is mutated in Leigh Syndrome, French Canadian type (LSFC). We utilize RNAi to engineer an allelic series of cellular models in which LRPPRC has been stably silenced to different levels of knockdown efficiency. Using expression profiling, we discovered a specific role for LRPPRC in the expression of all mitochondrial DNA (mtDNA)-encoded mRNAs, but not the rRNAs, without affecting nuclear genes encoding mitochondrial proteins.
2010-03-13 | GSE20847 | GEO
Project description:CircCDKN2B-AS1 interacts with IMP3 to stabilize Hexokinase 2 mRNA and facilitate cervical cancer aerobic glycolysis progression
| PRJNA612781 | ENA
Project description:The roles of RNA-binding proteins as chaperones in the lifecycles of mRNAs are not well understood. The mammalian mitochondrial genome has been compressed over evolution to a size of just 16 kb, nevertheless the expression of its genes requires transcription, RNA processing, translation and RNA decay, much like the more complex chromosomal systems, providing an opportunity to use it as a model system to understand the fundamental aspects of gene expression. Here we combine RNase footprinting with PAR-CLIP at unprecedented depth to reveal the importance of RNA-protein interactions guided by the LRPPRC/SLIRP complex in dictating RNA folding within the mitochondrial transcriptome. We show that LRPPRC, in complex with its protein partner SLIRP, binds throughout the mitochondrial transcriptome, with a preference for mRNAs, and its loss affects the entire secondary structure and stability of the transcriptome. We demonstrate that the LRPPRC/SLIRP complex is a global RNA chaperone that stabilizes RNA structures to expose the required sites for translation, stabilization and polyadenylation. Our findings reveal a general mechanism where extensive RNA-protein interactions ensure that RNA is accessible for its biological functions.
2017-11-21 | GSE100729 | GEO