PILAR1, a novel prognostic LncRNA, reveals the presence of a unique subtype of lung adenocarcinoma patients with KEAP1 mutations

Abstract

Lung Adenocarcinoma (LUAD) is the most common cause of lung cancer-related deaths. Long non-coding RNAs (LncRNAs) play an essential role in cancer development and progression. In this study, we identified PILAR1, a prognostic and overexpressed LncRNA, using multiple independent datasets of LUAD patients. Higher expression of PILAR1 was associated with survival in Dhanasekaran et al. (HR = 2.29, p-value = 0.017), TCGA (HR = 1.51, p-value = 0.017) and KM plotter (HR = 2.67, p-value $\le$ 0.0001) cohorts. Mutational landscape of LUAD showed that KEAP1 mutation was exclusively present in PILAR1 expressing samples. Further, knockdown of PILAR1 significantly inhibited cell proliferation, colony formation and migration of A549 cells. Importantly, inhibition of PILAR1 made the A549 cells more sensitive to etoposide. Furthermore, pathway analysis using differentially expressed genes in PILAR1 knockdown cells compared to control cells identified enrichment of DNA repair genes suggesting towards the mechanism of PILAR1 mediated etoposide sensitivity. Taken together, we identified a prognostically robust LncRNA, PILAR1, which also regulates cell growth in lung cancer cells. PILAR1 expression identified a novel subtype of LUAD patients with the exclusive KEAP1 mutation.

Seema Khadirnaikar

Research Scholar

My research interests include application of supervised and unupervised machine learning techniques to precision medicine.