Genome-wide profiling reveals cancer-related genes with switched alternative polyadenylation sites in colorectal cancer

Xiaochen Yang,1 Jun Wu,1 Wei Xu,1 Sheng Tan,2 Changyu Chen,3 Xiaoyan Wang,4 Jielin Sun,4 Yani Kang1 1School of Biomedical Engineering, Bio-ID Center, Shanghai Jiao Tong University, Shanghai, 200240, People’s Republic of China; 2The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, People’s Republic of China; 3Department of General Surgery, The First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei, Anhui, 230031, People’s Republic of China; 4Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, 200240, People’s Republic of China Background: Alternative polyadenylation (APA) is an important post-transcriptional regulation in eukaryotic cells. It plays considerable roles in many biological processes and diseases, such as cell differentiation, proliferation and cancer. Colorectal cancer (CRC) is one of the most common malignancies worldwide, which is among the top five in incidence and mortality of all cancers in China. Although there have been some studies on the APA of CRC, the normal and carcinoma samples used for genome-wide profiling were not matched. The purpose of this study was to obtain genes with switched 3'-untranslated region (UTR) that may be associated with intracellular regulation of CRC by analyzing APA patterns of strict control groups from clinical patients. Materials and methods: CRC and matched normal tissues were acquired from surgical specimens from three CRC patients. Their libraries of 3'-terminal fragments of mRNA with poly(A) tails were constructed by 3T-seq technology and sequenced by Illumina Hiseq X Ten. APA patterns of cancer and matched normal tissues were analyzed by bioinformatics analysis, and a representative gene, GPI, was verified by quantitative reverse transcription PCR. Results: Overall, we identified 35,076 poly(A) sites in total. Compared to the matched normal tissues, we detected 350, 405 and 375 genes with significantly APA-mediated 3'-UTR alteration in cancer tissues of three patients, respectively. Forty-seven genes with switched 3'-UTR were shared in all three patients. In addition, most of these genes have shortened 3'-UTRs, some of which were associated with cancers, such as GPI. Conclusion: Our studies found several genes with switched 3'-UTR in CRC patients, which may provide some important clues for more in-depth study of the cellular regulation in CRC from the perspective of post-transcriptional regulation. It may also help in the search for new biomarkers of CRC. Keywords: alternative polyadenylation, CRC, 3T-seq, 3'-UT