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| Status |
Public on Apr 08, 2020 |
| Title |
The long non-coding RNA PIK3CD-AS2 promotes lung adenocarcinoma progression via YBX1-mediated suppression of p53 pathway |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
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.
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| Overall design |
A549 cells were transfected with PIK3CD-AS2 siRNA or control, respectively. 48 hours after transfection, total RNA of A549 cells was harvested and analyzed by RNA sequencing (RNA-seq)
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| Contributor(s) |
Yin R, Zheng X |
| Citation(s) |
32165621 |
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| Submission date |
Feb 10, 2020 |
| Last update date |
Apr 08, 2020 |
| Contact name |
Rong Yin |
| Organization name |
Jiangsu Cancer Hospital
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| Street address |
42 baiziting
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| City |
nanjing |
| State/province |
-- None selected -- |
| ZIP/Postal code |
210009 |
| Country |
China |
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| Platforms (1) |
| GPL17303 |
Ion Torrent Proton (Homo sapiens) |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA605726 |
| SRA |
SRP247910 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE145018_All_Counts.xlsx |
1.2 Mb |
(ftp)(http) |
XLSX |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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