Abstract 51P
Background
Chromosomal instability (CIN) is hallmark of cancer associated to progression and aggressiveness in prostate cancer (PCa). In the search of the mechanisms controlling CIN, long non-coding RNAs (lncRNAs) have shown to play important roles in maintaining genome stability, nevertheless, characterization of these transcripts and the networks they control in CIN regulation is still poorly understood.
Methods
RNA-seq data from the prostate cell lines PrEC (stable) and LNCaP (unstable) was analyzed to find novel lncRNAs associated with CIN. Afterwards, experimental validation of the results in PrEC and LNCaP was performed with RT-qPCR and western blot. For the functional experiments, lncRNA knockdown (KD) was performed by transfecting cells with antisense oligonucleotides (ASOs) targeting the lncRNA of interest, followed by karyotyping to assess CIN in the transfected cells. Confirmation of the lncRNA KD was performed by qPCR.
Results
After analyzing and comparing RNA-Seq data from PrEC and LNCaP, a novel lncRNA was discovered in chromosome 3. This nuclear-retained transcript is adjacent to the protein coding gene RFC4, a gene associated to CIN that participates in DNA repair and replication. RT-qPCR analysis showed that while the lncRNA is upregulated in PrEC, RFC4 is downregulated, the opposite pattern was found in LNCaP, suggesting the lncRNA as a cis-repressor of RFC4. The functional experiments confirmed that the lncRNA is a transcriptional repressor of RFC4 but also a regulator of genome stability. After KD of the lncRNA in the stable cell line PrEC, an increase in RFC4 expression was observed as well as an increased number of tetraploid cells, suggesting CIN induction after lncRNA KD. To understand how the lncRNA regulates genome stability, RNA-Seq was performed in the KD experiments showing that lncRNA KD induced disruption of different pathways needed for proper DNA replication and chromosome segregation.
Conclusions
Together our results indicate that the novel lncRNA is a regulator of CIN through regulation of RFC4 and pathways important for maintaining genome stability. The lncRNA adjacent to the protein coding gene RFC4 could be a novel biomarker for PCa progression.
Editorial acknowledgement
Clinical trial identification
Legal entity responsible for the study
Unidad de Investigación Biomédica en Cáncer - Instituto Nacional de Cancerología - Instituto de Investigaciones Biomédicas - UNAM.
Funding
Unidad de Investigación Biomédica en Cáncer - Instituto Nacional de Cancerología - Instituto de Investigaciones Biomédicas - UNAM - CONACyT.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
114P - Circulating microRNAs and response to oncological and surgical therapy in patients with locally advanced gastric cancer
Presenter: Vasileia Kokala-Dimitropoulou
Session: Cocktail & Poster Display session
Resources:
Abstract
115P - BrainStorm-NSE: Serum neuron-specific enolase as a biomarker for central nervous system metastases: A prospective cohort study
Presenter: Diogo Martins-Branco
Session: Cocktail & Poster Display session
Resources:
Abstract
116P - Switching to a multigenic parallel sequencing approach: The landscape of biomarkers profiling changing between immunohistochemistry and next generation sequencing advantages and sustainability from a public hospital in Northern Italy
Presenter: Giulia Ghirardi
Session: Cocktail & Poster Display session
Resources:
Abstract
117P - Homologous recombination deficiency (HRD) by shallow whole genome sequencing (sWGS): Seamless integration in an existing NGS somatic oncology workflow
Presenter: Etienne Muller
Session: Cocktail & Poster Display session
Resources:
Abstract
118P - Molecular diagnostics of gastrointestinal stromal tumors in the era of precision oncology
Presenter: Alena Kalfusova
Session: Cocktail & Poster Display session
Resources:
Abstract
119P - De novo and histologically transformed small-cell lung cancer is sensitive to lurbinectedin treatment through the modulation of EMT and NOTCH signaling pathways
Presenter: Triparna Sen
Session: Cocktail & Poster Display session
Resources:
Abstract
120P - Anti-angiogenic therapy or immunotherapy? A multicenter real-world study of patients with advanced non-small cell lung cancer with EGFR / HER2 exon 20 insertion mutations
Presenter: Tianqing Chu
Session: Cocktail & Poster Display session
Resources:
Abstract
121P - Clinical outcomes of compound EGFR mutation in non-small cell lung cancer: A national, retrospective, multicenter study
Presenter: Aurélien Brindel
Session: Cocktail & Poster Display session
Resources:
Abstract
122P - Molecular testing, treatment, and response of patients with advanced solid tumors harboring an NTRK gene fusion: Second interim results of the REALTRK registry
Presenter: Sebastian Lange
Session: Cocktail & Poster Display session
Resources:
Abstract
123P - Incidence and outcomes of anaplastic lymphoma kinase (ALK) and ROS 1 positive advanced NSCLC: A real world experience
Presenter: Stalin Chowdary Bala
Session: Cocktail & Poster Display session
Resources:
Abstract