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LncRNA FENDRR-mediated tumor suppression and tumor-immune microenvironment changes in non-small cell lung cancer
Hongyu Pan1, Tao Yu1, Lei Sun1
1Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai, China.
Background:
Long noncoding RNAs (lncRNAs) play a key role in the development and progression of many cancer types, including lung cancer. The objective of this study is to examine the function and molecular mechanism of lncRNAs involved in non-small cell lung cancer (NSCLC).
Methods:
First, 7 lung cancer-related differentially expressed LncRNAs were screened from 2 genomic profiling datasets. Of these lncRNAs, FOXF1 adjacent noncoding developmental regulatory RNA (FENDRR) was found to be the only one that was both significantly down-regulated in the patients with advanced pathology and negatively correlated with prognosis. Thus, lncRNA FENDRR was further studied in this project. Clinical correlation analysis was further conducted in the GSE30219 dataset and 73 paired lung cancer and noncancerous tissues stored in our lab; Subsequently, we evaluated FENDRR coding potential with the Phylogenetic Codon Substitution Frequencies (PhyloCSF), Coding-Potential Assessment Tool (CPAT), and Coding Potential Calculator (CPC) online analytical tool. The cell growth ability was measured by CCK8 assay and clonogenicity assay, the metastatic capacities were evaluated using Transwell migration and invasion assays. Mechanistically, we analyzed the correlation of FENDRR function in NSCLC with immune response by utilizing The Cancer Genome Atlas (TCGA) data.
Results:
Results indicated a negative clinical correlation of FENDRR. Coding potential analysis showed FENDRR as a noncoding RNA. Elevated expression of FENDRR led to cell growth arrest, inhibition of proliferative ability, declined migration and invasion potential of NSCLC cells in vitro. Mechanistically, we discovered that FENDRR expression might be involved in aberrant immune response regulation.
Conclusions:
Taken together, our results provide a greater understanding of lncRNA FENDRR as a tumor suppressor with respect to tumor-immune interactions in NSCLC.
Insights
Long noncoding RNA FENDRR acts as a tumor suppressor in non-small cell lung cancer. Its reduced expression correlates with advanced disease, and it inhibits cell growth, migration, and invasion, potentially through immune interactions.
Area of Science:
- Oncology
- Molecular Biology
- Genomics
Background:
- Long noncoding RNAs (lncRNAs) are implicated in various cancers, including lung cancer.
- This study focuses on the role of lncRNAs in non-small cell lung cancer (NSCLC).
Purpose of the Study:
- To investigate the function and molecular mechanisms of lncRNAs in NSCLC.
- To identify specific lncRNAs involved in NSCLC progression and patient prognosis.
Main Methods:
- Screened 7 lung cancer-related lncRNAs from genomic datasets.
- Identified and analyzed lncRNA FENDRR (FOXF1 adjacent noncoding developmental regulatory RNA) for its clinical correlation, coding potential, and functional impact on NSCLC cells.
- Assessed cell growth, migration, and invasion in vitro, and analyzed immune response correlations using TCGA data.
Main Results:
- FENDRR was significantly downregulated in advanced NSCLC and negatively correlated with prognosis.
- FENDRR was confirmed as a noncoding RNA.
- Increased FENDRR expression inhibited NSCLC cell growth, proliferation, migration, and invasion in vitro.
- FENDRR expression is linked to aberrant immune response regulation in NSCLC.
Conclusions:
- lncRNA FENDRR functions as a tumor suppressor in NSCLC.
- FENDRR plays a role in tumor-immune interactions within NSCLC.
- Understanding FENDRR's mechanisms offers insights into NSCLC pathogenesis and potential therapeutic strategies.
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