Yunjing Zhang

Large-Scale Alternative Polyadenylation-Wide Association Studies to Identify Putative Cancer Susceptibility Genes

Abstract Alternative polyadenylation (APA) modulates mRNA processing in the 3′-untranslated regions (3′ UTR), affecting mRNA stability and translation efficiency. Research into genetically regulated APA has the potential to provide insights into cancer risk. In this study, we conducted large APA-wide association studies to investigate associations between APA levels and cancer risk. Genetic models were built to predict APA levels in multiple tissues using genotype and RNA sequencing data from 1,337 samples from the Genotype-Tissue Expression project. Associations of genetically predicted APA levels with cancer risk were assessed by applying the prediction models to data from large genome-wide association studies of six common cancers among European ancestry populations: breast, ovarian, prostate, colorectal, lung, and pancreatic cancers. A total of 58 risk genes (corresponding to 76 APA sites) were associated with at least one type of cancer, including 25 genes previously not linked to cancer susceptibility. Of the identified risk APAs, 97.4% and 26.3% were supported by 3′-UTR APA quantitative trait loci and colocalization analyses, respectively. Luciferase reporter assays for four selected putative regulatory 3′-UTR variants demonstrated that the risk alleles of 3′-UTR variants, rs324015 (STAT6), rs2280503 (DIP2B), rs1128450 (FBXO38), and rs145220637 (LDHA), significantly increased the posttranscriptional activities of their target genes compared with reference alleles. Furthermore, knockdown of the target genes confirmed their ability to promote proliferation and migration. Overall, this study provides insights into the role of APA in the genetic susceptibility to common cancers. Significance: Systematic evaluation of associations of alternative polyadenylation with cancer risk reveals 58 putative susceptibility genes, highlighting the contribution of genetically regulated alternative polyadenylation of 3′UTRs to genetic susceptibility to cancer.

Quality evaluation of HPV vaccine-related online messages in China: a cross-sectional study

Since 2019, three types of HPV vaccine have been approved for use in mainland China. High quality messages are crucial for vaccine acceptance, but little is known about the online information quality concerning HPV vaccine in China. "HPV vaccine" and "cervical cancer vaccine" in the form of Chinese were used as keywords through search engines from personal computer (PC), portable mobile device (PMD), and WeChat Public Accounts in 2019. Readability, information content, as well as DISCERN scores were evaluated for each message included. Characteristics associated with quality indicators of the messages were also analyzed. A total of 294 messages from PC engines (104, 35%), PMD engines (128, 43%) and WeChat (62, 21%) were assessed. Most (269, 91%) messages required at least undergraduate readability level. The most frequently reported theme was HPV vaccine and its function (273, 93%), while the least was information regarding quality, safety and side effects (129, 44%). The frequency of messages with at least one error was 132 (45%). The median of sum DISCERN scores was 42 (IQR = 14), and only one (< 1%) message showed good DISCERN quality. Messages retrieved from PC engines and those with pictures were of better overall quality. The overall quality of HPV vaccine-related online messages in Chinese websites was not optimal. Government and health professionals should promote information quality construction to improve the status of HPV vaccination messages online.