# In Silico Screening of Alternative Polyadenylation Regulators in Cancers

> **NIH NIH K01** · OREGON HEALTH & SCIENCE UNIVERSITY · 2020 · $142,721

## Abstract

PROJECT SUMMARY
Alternative polyadenylation (APA) enables the same gene to have multiple 3'UTR ends and affects more than
70% of human genes. By altering polyadenylation sites, APA can create transcripts with different cis-regulatory
elements to influence stability and translation. Accumulating evidence has indicated that APA is playing
important roles in cancers. For example, CCND1, an oncogene in leukemia, was found to use shorter 3'UTR to
escape miRNA repression in proliferating and transformed cells. Our study (Xia, Nature Communications)
observed global shortening of 3'UTR in hundreds of tumor samples. Therefore, APA regulators governing
widespread 3'UTR shortening in cancer may lead to drug target discoveries for cancer therapy. To this end,
our another study (Masamha Nature) identified CFIm25 as a master APA regulator in GBM. However, APA
regulators in other cancers still need to be explored. Recently, with the development of bioinformatics tools for
APA usage quantification from RNA-seq and wide employment of RNA-seq by large cancer genome
consortiums, it is possible to identify APA regulators through computational big data analysis. Our preliminary
analyses have identified DNMT3A, a highly mutated gene in acute myeloid leukemia (AML), as a potential APA
regulator in AML. Therefore, we hypothesize that a powerful and dedicated computational screening model can
be used to reveal APA regulators for cancers through integration APA usage with other molecular features,
including gene expression and DNA mutation. The objective of this proposal is to develop such a novel
computational method, and apply this method to infer APA regulators from ~15,000 tumor samples across 33
cancer types. These identified master APA regulator genes may sever as novel cancer driver/repressor genes
and thus provide new directions for therapeutic target discovery. My career goal is to develop and apply novel
computational and systems modeling methods for complex and large-scale clinical data analysis, by doing so,
provide novel molecular diagnosis and potential therapeutics for cancer and other diseases. Dr. Adam
Margolin, the director of the Computational Biology Program at Oregon Health & Science University (OHSU)
and Dr. Brian Druker, the director of OHSU's Knight Cancer Institute, will form a multidisciplinary mentoring
team to provided numerous educational opportunities to further enhance my research knowledge in both
computational biology and cancer biology. This K01 grant will offer me the protected time to develop essential
skills for independent research and the successful future grants application like NIH R01, and thus have a
long-term impact on my ability to sustain a career in computational cancer biology field.

## Key facts

- **NIH application ID:** 9924645
- **Project number:** 5K01LM012877-03
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Zheng Xia
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $142,721
- **Award type:** 5
- **Project period:** 2018-06-01 → 2021-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9924645

## Citation

> US National Institutes of Health, RePORTER application 9924645, In Silico Screening of Alternative Polyadenylation Regulators in Cancers (5K01LM012877-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9924645. Licensed CC0.

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