Abstract
Recently, a novel class of transcripts, long noncoding RNAs (lncRNAs), is involved in diseases including cancer. Here, we investigated the the role of lncRNA PANDAR in the progression of non-small cell lung carcinoma (NSCLC). PANDAR, interacting with NF-YA, was generally downregulated in NSCLC tissues. In a cohort of 140 NSCLC patients, decreased PANDAR expression was negatively correlated with greater tumor size (P<0.001) and advanced TNM stage (P=0.002). Moreover, PANDAR could serve as an independent predictor for overall survival in NSCLC (P=0.015). Further experiments demonstrated that PANDAR expression was induced by p53, and chromatin immunoprecipitation (ChIP) assays confirmed that PANDAR was a direct transcriptional target of p53 in NSCLC cells. PANDAR overexpression significantly repressed the proliferation in vitro and in vivo. We also showed that PANDAR-mediated growth regulation is in part due to the transcriptional modulation of Bcl-2 by interacting with NF-YA, thus affecting NSCLC cell apoptosis. To our knowledge, this is the first report which showed the role of PANDAR in the progression of NSCLC. The p53/PANDAR/NF-YA/Bcl-2 interaction might serve as targets for NSCLC diagnosis and therapy.
Highlights
The investigation of mechanisms of tumorigenesis mainly focused on protein-coding genes
For each individual molecule, it needs to be further confirmed whether long noncoding rna (lncRNA) could execute important functions or just represent transcriptional noise or background transcription; for the majority of lncRNAs, their conservative evolution reveals that they might be functional.[26]
We explored the correlation between PANDAR levels and clinico-pathological characteristics as well as the prognosis in patients with non-small cell lung cancer (NSCLC)
Summary
The investigation of mechanisms of tumorigenesis mainly focused on protein-coding genes. NF-YA is closely related to tumorigenesis;[21,22] and the role of PANDAR in lung cancer has not been investigated. These prompted us to explore the role of PANDAR in human NSCLC. We found that lncRNA PANDAR was significantly downregulated in NSCLC tissues than that in Abbreviations: lncRNA, long noncoding rna; PANDAR, promoter of CDKN1A antisense DNA damage activated RNA; NF-YA, nuclear transcription factor Y, alpha; NSCLC, non-small cell lung carcinoma; Bcl-2, B-cell CLL/lymphoma 2; ChIP, Chromatin Immunoprecipitation; RIP, RNA immunoprecipitation. We demonstrated that PANDAR could modulate the BCL2 by binding to NF-YA, which may partly account for PANDAR-mediated apoptosis regulation, affecting the proliferation of NSCLC both in vitro and in vivo
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