|
| Status |
Public on Mar 01, 2019 |
| Title |
LINC00261 is an epigenetically-regulated tumor suppressor that is essential for activation of the DNA damage response (AEC/LUAD RNA-seq data set) |
| Organism |
Homo sapiens |
| Experiment type |
Non-coding RNA profiling by high throughput sequencing
|
| Summary |
Lung cancer is the leading cause of cancer-related death in the United States. Long non-coding RNAs (lncRNAs) are a class of regulatory molecules whose role in lung carcinogenesis is poorly understood. In this study, we profiled lncRNA expression in lung adenocarcinoma (LUAD) cell lines, compared their expression to that of purified alveolar epithelial type II cells (the purported cell of origin for LUAD), cross-referenced these with lncRNAs altered in primary human tumors, and interrogated for lncRNA whose expression correlated with patient survival. We identified LINC00261, a lncRNA with unknown function in LUAD, adjacent to the pioneering transcription factor FOXA2. Loss of LINC00261 was observed in multiple tumor types, including liver, breast, and gastric cancer. Reintroduction of LINC00261 into human LUAD cell lines inhibited cell migration and slowed proliferation by inducing a G2/M cell cycle arrest while upregulating DNA damage pathway genes and inducing phosphorylation-mediated activation of components of the DNA damage pathway. FOXA2 was able to induce LINC00261 expression, and the entire locus underwent hypermethylation in LUAD, leading to loss of expression. We have thus identified an epigenetically deregulated lncRNA, whose loss of expression in LUAD promotes the malignant phenotype and blocks activation of the DNA damage machinery, predisposing lung cells to cancer development.
|
| |
|
| Overall design |
Primary AEC isolated from three human donor remnant transplant lungs and sixteen (16) lung adenocarcinoma cell lines. Note that PC3 and PC9 are lung adenocarcinoma cell lines from Japan, NOT prostate cancer cell lines
|
| Web link |
http://cancerres.aacrjournals.org/content/early/2019/02/22/0008-5472.CAN-18-2034.long
|
| |
|
| Contributor(s) |
Shahabi S, Kumaran V, Castillo J, Cong Z, Nandagopal G, Mullen DJ, Alvarado A, Correa MR, Saizan A, Goel R, Bhat A, Lynch SK, Zhou B, Borok Z, Marconett C |
| Citation(s) |
30796052 |
| NIH grant(s) |
| Grant ID |
Grant title |
Affiliation |
Name |
| P30 CA014089 |
USC Norris Comprehensive Cancer Center (Core) Grant |
UNIVERSITY OF SOUTHERN CALIFORNIA |
PEGGY J Farnham |
| R35 HL135747 |
Beyond the barrier: alveolar epithelial cell biology in health and disease |
UNIVERSITY OF SOUTHERN CALIFORNIA |
Zea Borok |
| R01 HL114959 |
Epithelial abnormalities in IPF: role of ER stress and GRP78/BiP |
UNIVERSITY OF SOUTHERN CALIFORNIA |
Beiyun Zhou |
|
| |
| Submission date |
Feb 01, 2018 |
| Last update date |
Jul 17, 2023 |
| Contact name |
Crystal N Marconett |
| E-mail(s) |
cmarcone@usc.edu, cmarconett@coh.org
|
| Phone |
626-218-4357
|
| Organization name |
City of Hope
|
| Department |
Integrative Translational Sciences
|
| Lab |
Crystal Marconett
|
| Street address |
1500 E Duarte Rd
|
| City |
Duarte |
| State/province |
CA |
| ZIP/Postal code |
91010 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
|
| Samples (19)
|
|
| This SubSeries is part of SuperSeries: |
| GSE110025 |
LINC00261 is an epigenetically-regulated tumor suppressor that is essential for activation of the DNA damage response |
|
| Relations |
| BioProject |
PRJNA432576 |
Less...
More...