# Chimeric RNAs and their implication in lymphatic metastasis of bladder cancer

> **NIH NIH R01** · UNIVERSITY OF VIRGINIA · 2021 · $205,913

## Abstract

PROJECT SUMMARY
Bladder cancer represents a common malignancy worldwide. The main cause of death in bladder cancer
patients is metastasis, with lymphatic metastasis as the primary means. Metastatic bladder cancer is currently
difficult to remove completely, and not sensitive to radiotherapy and chemotherapy. Better understanding and
exploitation of new diagnostic and therapeutic strategy for lymphatic metastasis of bladder cancer is urgently
needed. The study of gene fusions has founded the theoretical backgrounds for many cancer diagnosis and
therapeutics. However, even with whole genome sequencing, novel recurrent gene fusions are rarely identified
in bladder cancer. Recently, our work on RNA trans-splicing and intergenic cis-splicing have helped open a
new paradigm for intergenic splicing processes that generate chimeric RNAs with pro-tumorigenic activities,
and may explain the molecular basis of the presence of driver onco-fusion products in the absence of
chromosomal rearrangement at the DNA level. Indeed, in our preliminary studies, we have identified several
chimeric RNAs unique to bladder cancer, but produced by intergenic splicing. Within a month since the issue of
the RFA, together with our Chinese collaborators, we have successfully identified a few chimeric RNAs that are
differentially expressed in lymph node metastatic group using only partial data. This success plus our past
fruitful collaboration encouraged us to propose the following aims: 1. To identify of chimeric RNAs associated
with lymphatic metastasis of bladder cancer by combining the RNA-Sequencing data from TCGA and China.
By integrating with CPTAC and whole genome sequencing data associated with TCGA, we can determine
whether the chimeric RNAs may code for chimeric protein, and whether they are products of gene fusion or
intergenic splicing. Using the clinical information from TCGA and Chinese patients, we will reveal the
relationship between chimeric RNAs and lymphatic metastasis, disease progression, and prognosis; 2. To
investigate the role of the chimeric RNAs in lymphatic metastasis of bladder cancer cells, and to elucidate the
molecular mechanism of the chimeric RNAs in regulating lymphatic metastasis of bladder cancer; We will focus
on two groups of chimeric RNAs, fusion protein-coding and long non-coding chimeric RNA (lnccRNA). 3. To
explore the significance of chimeric RNA as an early diagnostic marker, prognostic factor, and therapeutic
target for lymphatic metastasis of bladder cancer. We will investigate the potential of the candidate chimeric
RNAs as biomarkers, and nanoparticle delivery of siRNAs to target key chimeric RNAs; and 4) To develop an
interactive web-based database to disseminate the results. The proposed study fits the NCI Funding Priorities,
Genomics/Epigenomics/Transcriptomics/Proteomics, in that we will combine the large multi-omics data from
both countries, analyze the landscape of chimeric RNAs, and investigate their roles as protein-coding...

## Key facts

- **NIH application ID:** 10110000
- **Project number:** 5R01CA245905-02
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** HUI LI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $205,913
- **Award type:** 5
- **Project period:** 2020-03-01 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10110000

## Citation

> US National Institutes of Health, RePORTER application 10110000, Chimeric RNAs and their implication in lymphatic metastasis of bladder cancer (5R01CA245905-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10110000. Licensed CC0.

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