Abstract 1822: A mitochondrial pfeRNA associates with Far Upstream Element Binding Protein 1 (FUBP1) to promote lung adenocarcinoma tumorigenesis

Background: Protein Functional Effector RNAs (pfeRNAs) are novel small non-coding RNA molecules with great prognostic and diagnostic potential for NSCLC. They feature direct binding to, and regulation of phosphorylated proteins involved in lung cancer tumorigenesis pathways. Using next-generation sncRNA deep sequencing, we have identified a mitochondrial pfeRNA (mtpfeRNA) that could play a key role in tumorigenesis and cancer development of lung adenocarcinoma (ADC). Methods: Using next-generation sncRNA deep sequencing, we analysed ADC and human normal bronchial epithelial (HBE) cell lines; and biospecimens including matched biopsy-proven ADC tissue, histologically normal adjacent lung tissue, benign lymph node, and (iv) malignant lymph nodes; Identifying a mitochondrial pfeRNA that could play critical roles in lung cancer tumorigenesis. Next, we examined the impact of this mtpfeRNA on lung ADC cell line viability. Liquid chromatography-tandem mass spectrometry analysis and reverse immunoprecipitation assays were used to identify critical interacting protein partners known to drive tumorigenesis. We further correlated our findings to clinical staging of ADC tumor cores by IHC staining. Results: The expression levels of mtpfeRNA were upregulated in ADC compared to that of squamous cell carcinoma and normal human bronchial epithelial cells. We also noted that blocking the upregulated mtpfeRNA resulted in significant decreases in cell viability in ADC cells. Next, we determined that mtpfeRNA binds to Far Upstream Element Binding Protein 1 (FUBP1). Furthermore, we confirmed that both mtpfeRNA and FUBP1 expression correlated to stages and lymph node metastasis in patients with ADC. Conclusion: We revealed novel functions of a mtpfeRNA in ADC, providing potential molecules for developing diagnostics and targeted therapy to improve the dismal survival rate of patients with ADC. Citation Format: Nadege T. Fackche, Yuping Mei, Tomoaki Ito, Matthew Garner, Malcolm Brock. A mitochondrial pfeRNA associates with Far Upstream Element Binding Protein 1 (FUBP1) to promote lung adenocarcinoma tumorigenesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1822.