Genome-wide profiling reveals alternative polyadenylation of mRNA in human non-small cell lung cancer

Background Lung cancer is the second most common cancer with an extremely poor overall survival rate. Post-transcriptional regulation of gene expression play many important roles in human cancer, and one of the potential mechanisms underlying this is alternative mRNA maturation at its 3 ' untranslated regions (3 '-UTRs). Methods Cancer tissues and paired adjacent normal lung tissues from 26 patients diagnosed with non-small cell lung cancer (NSCLC) were analyzed by in vitro transcription-sequencing alternative polyadenylation sites (IVT-SAPAS). 41,773,101 reads in average were obtained from each paired sample. A potential regulation of Cleavage Stimulation Factor Subunit 2 (CSTF2) on 3 ' UTR length of genes was tested in H460 cells. Results 1439 (10.26%) genes showed up-regulated expression and 1364 (9.72%) genes showed down-regulated expression in lung cancer tissue versus normal lung tissue, and shorten 3 ' UTR in cancer tissue was detected in cancer tissues collected from 96.2% (25/26) patients, indicating lung cancer tend to have shortened 3 ' UTRs of these identified genes. KEGG analysis showed 1855 genes with shorten 3 ' UTR were enriched in mTOR signaling, ubiquitin mediated proteolysis and RNA degradation. Knocking down CSTF2 expression in H460 cells results in 3 ' UTR elongation of genes that was identified to be with shortened length in cancer tissues. Conclusion Alternative polyadenylation (APA) site-switching of 3 ' UTRs is prevalent in NSCLC, and CSTF2 may serve as an oncogene regulates the 3 ' UTR length of cancer related genes in NSCLC.