GSE66186
smRNA sequencing analysis to identify p53-dependent non-coding RNA networks in Chronic Lymphocytic Leukemia
Mutations of the tumor suppressor p53 lead to chemotherapy resistance and a dismal prognosis in chronic lymphocytic leukemia (CLL). Comparing miRNA/non-coding RNA expression profiles between p53 wild-type and p53 mutant samples in response to DNA damage, we exploit the impaired transcriptional activity of mutant p53 to map out p53 targets in primary CLL by small RNA sequencing. Focusing on miRNAs, we identify a set of p53-dependent miRNAs (miR-182-5p, miR-7-5p, miR-320c/d) in addition to the key p53 target miR-34a. Beyond miRNAs, the long non-coding RNAs (lncRNAs) NEAT1 and lincRNA-p21 are induced in response to DNA damage in the presence of functional p53 but not in CLL with p53 mutation. Overall design: Quantification of mature miRNA, other ncRNA and mRNA expression profiles in 68 paired CLL primary samples 24h after irradiation or no treatment.