Abstract
BackgroundLung 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).MethodsCancer 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.Results1439 (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.ConclusionAlternative 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.
Highlights
Lung cancer is the second most common cancer and the leading cause of cancer-related death for both man and woman worldwide, with an extremely poor overall survival rate, 5-year survival rate is only approximate 18% [1]
KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analysis further revealed that the up-regulated genes in cancer tissues were enriched in signaling pathways primarily associated with cell cycle and biosynthesis of amino acids (Fig. 1c), and the downregulated genes were enriched in pathways of neuroactive ligand-receptor interaction and cytokine–cytokine receptor interaction (Fig. 1d)
Cleavage Stimulation Factor Subunit 2 (CSTF2) regulates 3′ untranslated regions (3′untranslated regions (UTR)) shortening in non-small cell lung cancer (NSCLC) cell To assess the potential mechanisms of 3′UTR shortening in human lung cancer, we examined the RNA expression of genes (Additional file 1: Table S3) that their encoding proteins may correlate to 3′UTR length editing
Summary
Lung cancer is the second most common cancer and the leading cause of cancer-related death for both man and woman worldwide, with an extremely poor overall survival rate, 5-year survival rate is only approximate 18% [1]. Zhang et al J Transl Med (2019) 17:257 genetic alterations, post-transcriptional regulation of gene expression play many important roles in cancer development and progression, and one of the potential mechanisms underlying this is alternative mRNA maturation at its 3′ untranslated regions (3′-UTRs) which leads to distinct mRNA isoforms from the same gene [6, 7]. The formation of 3′-UTRs through polyadenylation process of sequential addition of a poly(A) tail on 3′ end of precursor mRNA is the last key step in mRNA maturation process [9]. Posttranscriptional 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)
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