Genomic characteristics of RARRES1 wild type and knockout mice lung tissues

Purpose: RARRES1 is proposed as tumor suppressor gene but its function is not clear yet. To elucidate RARRES1 function in carcinogenesis, we examine phenotype and genetic characteristics of the RARRES1 genetically knockout mice lung.Methods: Genetic profiles of RARRES1 wild type and knockout mouse lung tissues of embryonic day 19.5, 10-month-old, and 18-month-old mice were analyzed by whole genome and RNA sequencing in triplicate, using Illumina Hiseq X ten. Additionally, three lung tumors originated from RARRES1 knockout mice also examine using same platform.Results: RARRES1 knockout accelerate spontaneous lung carcinogenesis, with pluripotency of stem cells, Hippo signaling pathway, Wnt signaling pathway, and cell cycle related genes are significantly activated including Nanog, CDK1, Cyclin E. In addition, RARRES1 knockout induced lung cancer had rare oncogenic mutations, on the contrary, lung tissue progenitor cell, lung bipotent progenitor cell and AT2 type cell popularity increased.Conclusions: RARRES1 knockout accelerate spontaneous lung carcinogenesis through organ stem cell population enhancement with various stemness related gene set activation beside rare mutational driving.