# MiRNAs in hepatocellular carcinoma development and treatment

> **NIH NIH R01** · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · 2021 · $410,875

## Abstract

Hepatocellular carcinoma (HCC) is the most common malignant tumor of the liver and the third leading cause
of death from cancer. However, currently there is no effective treatment for HCC. It is therefore urgent to
develop novel therapeutic approaches for the treatment of HCC. Increasing evidence suggests that being able
to modulate specific miRNAs may lead to the development of novel cancer therapies. Our studies (and others)
indicate that a microRNA, miR-26a, represses proinflammatory cytokines, especially interleukin 6 (IL-6) and its
downstream mediator, signal transducer and activator of transcription 3 (STAT3), suggesting a tumor
suppressive role of miR-26a on HCC development. However, the role of miR-26a in HCC development in the
setting consisting of both hepatocytes and Kupffer cells in appropriate HCC mouse models has not been
determined. Furthermore, whether modulating miR-26a in hepatocytes and/or Kupffer cells can be an effective
therapeutic approach for treating HCC has not been tested. The objective of this proposal is to investigate the
molecular and cellular mechanisms by which miR-26a overexpression in hepatocytes and Kupffer cells inhibits
HCC development. In addition, we have identified small molecules and developed siRNA/RNA in vivo targeted
delivery technology that can increase miR-26a expression in the liver. In Aim 1, we will determine the effect of
overexpression of miR-26a in hepatocytes and in Kupffer cells on suppression of HCC development. We have
generated hepatocyte-specific as well as Kupffer cell-specific miR-26a overexpression transgenic mice. We will
use these unique transgenic mouse lines to define the cellular and molecular mechanisms by which miR-26a
exerts its effect on HCC. In Aim 2, we will determine the effect of small molecules on miR-26a induction and
HCC suppression. We have also developed an innovative siRNA/RNA in vivo targeted delivery technology--
CpG-siRNA/RNA—that enables RNA in vivo delivery into Toll-like Receptor 9-positive Kupffer cells and
inflammatory/malignant hepatocytes. CpG-Stat3 siRNA is moving towards clinical trials for glioma and
lymphoma patients at City of Hope. We will assess the effect of both CpG-miR-26a and CpG-Stat3 siRNA on
HCC development in hepatocytes or/and Kupffer cells in animal models. The proposed studies will not only
provide mechanistic insights into pathways underlying HCC but also help to develop effective treatment
strategies for HCC.

## Key facts

- **NIH application ID:** 10070574
- **Project number:** 5R01CA139158-10
- **Recipient organization:** BECKMAN RESEARCH INSTITUTE/CITY OF HOPE
- **Principal Investigator:** WENDONG HUANG
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $410,875
- **Award type:** 5
- **Project period:** 2011-01-25 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10070574

## Citation

> US National Institutes of Health, RePORTER application 10070574, MiRNAs in hepatocellular carcinoma development and treatment (5R01CA139158-10). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10070574. Licensed CC0.

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