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The long non-coding RNA PIK3CD-AS2 promotes lung adenocarcinoma progression via YBX1-mediated suppression of p53 pathway

ABSTRACT: The long non-coding RNA PIK3CD-AS2 promotes lung adenocarcinoma progression via YBX1-mediated suppression of p53 pathway

PROVIDER: PRJNA605726 | ENA |

REPOSITORIES: ENA

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The long non-coding RNA PIK3CD-AS2 promotes lung adenocarcinoma progression via YBX1-mediated suppression of p53 pathway

Project description:The underlying mechanisms of long non-coding RNAs (lncRNA) participating in the progression of lung cancers are largely unknown. We found a novel lncRNA, PIK3CD antisense RNA 2 (PIK3CD-AS2), that contributes to lung adenocarcinoma (LUAD) progression. The expression characteristics of PIK3CD-AS2 in LUAD were analyzed using microarray expression profile, The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets, and validated in 92 paired LUAD tissues by chromogenic in situ hybridization. Our data confirmed that PIK3CD-AS2 expression is a crucial regulator of LUAD progression and associated with shorter patient survival. In vitro studies showed that PIK3CD-AS2 increased cell growth and slowed apoptosis in p53wt cells but not in p53null cells. Mechanically, it is demonstrated that PIK3CD-AS2 bound to and maintained the stability of Y-box binding protein 1 (YBX1), a potent destabilizer of p53, by impeding its ubiquitination and degradation. Downexpression of YBX1 reversed PIK3CD-AS2-mediated inhibition of p53 signaling. Additionally, the therapeutic effect evaluation of a Locked Nuclear Acid (LNA) specifically targeting PIK3CD-AS2 showed an anti-tumor activity in mice with A549 cells xenograft and p53 wild-type LUAD patient-derived tumor xenograft (PDTX) model. Clinically, the high expression of PIK3CD-AS2 showed a poor disease-free survival in p53 wild-type patients in TCGA database. Our findings suggest that PIK3CD-AS2 regulates LUAD progression and elucidate a new PIK3CD-AS2/YBX1/p53 signaling axis, providing a potential lncRNA-directed therapeutic strategy especially in p53 wild-type LUAD patients.

2020-04-08 | GSE145018 | GEO

The long non-coding RNA PIK3CD-AS2 promotes lung adenocarcinoma progression via YBX1-mediated suppression of p53 pathway.

Project description: Not available

| S-EPMC7067885 | biostudies-literature

Analysis of genes regulated by AS1 and AS2

Project description:AS1 and AS2 encode MYB related protein and AS2-domain containing protein, respectively and may regulate transcription. These genes are involved in the determination of axes of leaves of Arabidopsis thaliana. To know the gene regulation in the leaf development, expression profile among wild-type, as1 and as2 mutants and AS2 overexpression plants were compaired. shoot apices from as1-1, as2-1, AS2 overexpressing, and wild type embryos

2013-03-01 | E-GEOD-44028 | biostudies-arrayexpress

YBX1 HITS-CLIP

Project description:In order to identify YBX1 binding sites on endogenous RNA, we performed HITS-CLIP on endogenous YBX1 We used a previously published method to perform HITS-CLIP on endogenous YBX1 (Licatalosi D, et al. 2008, Nature 456:464-U22)

2015-05-08 | E-GEOD-63604 | biostudies-arrayexpress

YBX1 small-RNA HITS-CLIP

Project description:In order to identify YBX1 binding sites on tRNA fragments, we performed small-RNA HITS-CLIP on endogenous YBX1 We used a previously published method to perform HITS-CLIP on endogenous YBX1 (Chi SW, et al. 2009, Nature 460:479)

2015-05-08 | E-GEOD-63597 | biostudies-arrayexpress

Chip-chip from HCT116 cells with YBX1

Project description:YBX1 is a multifunctional protein involved in the control of transcription and translation. We identified YBX1 as an target of MEK/ERK signaling in colorectal cancer cell lines. We performed a ChIP-chip analysis of HCT116 cells to identify new potential target genes of YBX1. Comparison of input DNA fragments with fragments coprecipitated with YBX1 in HCT116 cells.

2010-10-09 | E-GEOD-18337 | biostudies-arrayexpress

YBX1-dependent hypoxia-induced modulation of gene expression

Project description:In order to identify YBX1-dependent targets that are modulated under hypoxic conditions, we used control and YBX1 knockdown cells grown under normoxia and hypoxia to profile gene expression levels. Control and YBX1-knockdown cells were grown and profiled under hypoxia and normoxia to identify YBX1-dependent hypoxia-induced target transcripts.

2015-05-08 | E-GEOD-63562 | biostudies-arrayexpress

Analysis of genes regulated by AS2 and TOP1

Project description:AS2 encode AS2-domain containing protein and may regulate transcription. AS2 is involved in the determination of axes of leaves of Arabidopsis thaliana. Type IB DNA topoisomerase (TOP1α) gene has genetic interaction with AS1 and AS2 and is involved in repression of leaf polarity genes. To know the gene regulation in the leaf development, expression profile among wild-type and as2 mutant treated with and without 10-hydroxyl substituted camptothecin (10H-CPT), a specific TOP1 inhibitor, were compared

2022-12-21 | GSE125138 | GEO

Analysis of genes regulated by AS1 and AS2

2013-03-01 | GSE44028 | GEO

KIMAT1 and HIF1A-As2 silencing RNA-seq

Project description:In our study, we valided the important oncogeneic roles of KIMAT1 and HIF1A-As2 in non-small cell lung cancer. We used custom designed GapmeRs to silence the KIMAT1 and HIF1A-As2 in H1299 and performed RNA-seq. 11389 and 7767 genes were regulated by KIMAT1 and HIF1A-As2, respectively.

2020-12-17 | GSE124628 | GEO

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