# Explore piRNA as a novel therapeutics for hepatocellular carcinoma

> **NIH NIH R21** · YALE UNIVERSITY · 2020 · $218,588

## Abstract

Abstract
The goal of the proposed study is to demonstrate the viability of a novel Piwi-interacting RNA (piRNA)-based
therapeutic strategy for the treatment of hepatocellular carcinoma (HCC). piRNAs are an abundant class of small
(26-31 nt) non-coding RNAs with approximately 23,000 known human members and play a pivotal role in the
maintenance of genomic stability in germ cells via epigenetic silencing of transposable elements (TE). Recent
evidence from our group and others has suggested that piRNAs can also induce DNA methylation at non-TE
protein-coding genes, including cancer-related genes in somatic cells. However, the role of piRNAs in human
cancers has not been fully studied and no previous publication has explored the use of piRNA as a therapeutic
tool. Our previous analyses have detected marked differences in expression of several piRNAs between normal
liver tissue and HCC tissue as well as anti-cancer effects of an exogenously modulating expression of one of
these identified piRNAs. In the proposed study, we seek to expand upon these important findings by further
examining the potential anticancer impact in vivo for the candidate piR-37213. Specifically, we will first examine
the anti-tumor effect of piR-37213 on HCC cells in vivo using an orthotopic mouse xenograft model (Specific Aim
1), which allows us to test whether the observed anti-proliferative effects in vitro can be replicated in live animals.
We will also examine molecular mechanisms accounting for the anti-tumor effect of piR-37213 (Specific Aim 2).
In this Aim, we will first perform a genome-wide expression profiling study to reveal the gene regulation network
and global impact of piR-37213, and confirm these findings with relevant in vitro assays if applicable. Next, we
will perform a RNA pull-down assay to explore potential piRNA binding sequences. This study represents the
key first step in the development of an innovative, piRNA-based therapeutic strategy that may be utilized as a
personalized treatment approach via the restoration of normal piRNA expression on an individual basis.
Knowledge obtained from this study will advance our understanding of a novel mechanism underlying HCC
biology, expand knowledge of the role and function of piRNA in tumorigenesis, and provide new avenues of
research that can be exploited to facilitate the development of novel therapeutic strategies.

## Key facts

- **NIH application ID:** 9868923
- **Project number:** 5R21CA238100-02
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** YONG ZHU
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $218,588
- **Award type:** 5
- **Project period:** 2019-02-08 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9868923

## Citation

> US National Institutes of Health, RePORTER application 9868923, Explore piRNA as a novel therapeutics for hepatocellular carcinoma (5R21CA238100-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9868923. Licensed CC0.

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