Alternative polyadenylation is associated with lower expression of PABPN1 and poor prognosis in non-small cell lung cancer.
Bottom Line: We established and evaluated the APA score by quantitative RT-PCR in 147 clinical specimens of non-small cell lung cancer and compared the results with the clinical outcomes and expression levels of APA-related genes, including PABPN1, CPEB1, E2F1 and proliferation markers (MKI67, TOP2A and MCM2).Moreover, the APA score was correlated with the maximum standardized uptake value of the tumors on positron emission tomography (r = 0.53; P < 0.001).Our results indicate that the loss of PABPN1, a suppressor of APA, might promote tumor aggressiveness by releasing the cancer cells from microRNA-mediated gene regulation.
Affiliation: Department of Thoracic Surgery, University of Tokyo Hospital, Tokyo, Japan.Show MeSH
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Mentions: Using the rmodel, we selected 16 genes that showed 3′UTR shortening in more than 20 of the 40 lung adenocarcinoma specimens included within the GSE10245 dataset (Table S3). All 16 genes showed 3′UTR shortening in more than 10 of the 18 lung squamous cell carcinoma specimens within the GSE10245 dataset (Table S3). The APA status of the 16 genes was confirmed in 7 clinical lung cancer specimens and 8 normal lung tissue specimens (Fig.3), and the top 10 genes which showed more marked APA in lung cancer were selected as the APA-indicator genes (C1orf52, DIEXF, ESYT2, HN1L, MUC20, NDFIP2, RBM33, SCAMP1, SMC1A and SSR1). For subsequent analysis, we defined the APA score as the total number of genes that showed 3′UTR shortening among the 10 APA-indicator genes.
Affiliation: Department of Thoracic Surgery, University of Tokyo Hospital, Tokyo, Japan.