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Published on: October 27, 2014
The pseudogene-derived long noncoding RNA SFTA1P is down-regulated and suppresses cell migration and invasion in lung
Hua Zhang1, Yaqiong Xiong2, Rui Xia3
11 Department of Joint Trauma, Junan County People's Hospital, Linyi, People's Republic of China.
Abstract:
Pseudogenes were once considered to be genomic fossils without biological function. Interestingly, recent evidence showed that a lot of pseudogenes are transcribed in human cancers, and their alterations contribute to multiple cancer development and progression. It is apparent that many pseudogenes transcribe noncoding RNAs and contribute to the role noncoding genome plays in human cancers. On this basis, some pseudogene transcripts are currently ranked among the classes of long noncoding RNAs. In this study, we identified a new pseudogene-derived long noncoding RNA termed SFTA1P by analyzing the microarray data of non-small cell lung cancer from Gene Expression Omnibus datasets. We found that SFTA1P expression was significantly decreased in non-small cell lung cancer tissues compared with normal tissues in non-small cell lung cancer microarray data. Moreover, decreased SFTA1P expression is only correlated with lung adenocarcinoma patients' poor survival time but not with lung squamous cell carcinoma patients' survival. In addition, gain-of-function studies including growth curves, migration, invasion assays, and in vivo studies were performed to verify the tumor suppressor role of SFTA1P in non-small cell lung cancer. Finally, the potential underlying pathways involved in SFTA1P were investigated by analyzing the SFTA1P-correlated genes in The Cancer Genome Atlas lung adenocarcinoma and normal tissues RNA sequencing data. Taken together, these findings demonstrate that pseudogene-derived long noncoding RNA SFTA1P exerts the tumor suppressor functions in human lung adenocarcinoma. Our investigation reveals the novel roles of pseudogene in lung adenocarcinoma, which may serve as a new target for lung adenocarcinoma diagnosis and therapy.
Insights
Pseudogenes, once thought functionless, are transcribed in cancers. This study identifies SFTA1P, a pseudogene-derived long noncoding RNA, as a tumor suppressor in lung adenocarcinoma, potentially aiding diagnosis and therapy.
Area of Science:
- Genomics
- Cancer Biology
- Noncoding RNA Research
Background:
- Pseudogenes were historically considered non-functional genomic relics.
- Emerging evidence highlights pseudogene transcription in human cancers, influencing disease development.
- Pseudogene transcripts, including long noncoding RNAs (lncRNAs), play roles in cancer progression.
Purpose of the Study:
- To identify and characterize novel pseudogene-derived lncRNAs in non-small cell lung cancer (NSCLC).
- To investigate the functional role and clinical significance of the identified pseudogene SFTA1P in NSCLC, particularly lung adenocarcinoma.
- To explore the molecular pathways associated with SFTA1P in lung adenocarcinoma.
Main Methods:
- Analysis of Gene Expression Omnibus (GEO) microarray data for NSCLC.
- Differential expression analysis of SFTA1P in NSCLC tissues versus normal tissues.
- Gain-of-function studies (in vitro and in vivo) to assess SFTA1P's tumor suppressor activity.
- Correlation analysis of SFTA1P expression with patient survival data.
- Investigation of SFTA1P-associated genes using The Cancer Genome Atlas (TCGA) RNA sequencing data.
Main Results:
- SFTA1P was identified as a novel pseudogene-derived lncRNA.
- SFTA1P expression was significantly downregulated in NSCLC tissues.
- Decreased SFTA1P expression correlated with poorer survival in lung adenocarcinoma patients, but not lung squamous cell carcinoma.
- Functional studies confirmed SFTA1P's tumor suppressor role in NSCLC by inhibiting growth, migration, and invasion.
- Potential molecular pathways influenced by SFTA1P in lung adenocarcinoma were elucidated.
Conclusions:
- Pseudogene-derived lncRNA SFTA1P functions as a tumor suppressor in human lung adenocarcinoma.
- SFTA1P represents a novel potential biomarker for lung adenocarcinoma diagnosis.
- SFTA1P may offer a new therapeutic target for lung adenocarcinoma treatment.
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