# The Long Noncoding RNA MALAT1 in Liver Cancer

> **NIH NIH R01** · TULANE UNIVERSITY OF LOUISIANA · 2020 · $347,034

## Abstract

Project Description
 Hepatocellular carcinoma (HCC) is the fifth most common human cancer and the
third leading cause of cancer-related death. The tumors usually develop in the
background of chronic liver diseases with inflammation, tissue injury and disregulated
hepatocyte regeneration. Recent whole-genome sequencing analyses have identified
MALAT1 as a frequently mutated long noncoding RNA (lncRNA) in human HCC,
although the mechanism by which MALAT1 regulates hepatic carcinogenesis remains
unknown. The current application is proposed to investigate the biological functions and
molecular mechanisms of MALAT1 in HCC. We hypothesize that MALAT1 is a pivotal
long non-coding RNA that drives hepatic carcinogenesis through formation of a lncRNA-
protein complex that terminates TGF-β/R-Smad signaling and through interaction with
chromatin-modifying proteins thus regulating liver cancer gene expression. We further
postulate that inhibition of MALAT1 and related signaling molecules may represent an
effective therapeutic strategy for HCC treatment. These hypotheses will be evaluated
by complementary in vitro biochemical and molecular analyses and in vivo animal
models. We propose two interrelated specific aims. Specific Aim 1 is designed to
delineate the effect and mechanism of MALAT1 in liver carcinogenesis. Experiments
will be carried out to evaluate the hypothesis that MALAT1 promotes liver
carcinogenesis through formation of a lncRNA-protein complex that facilitates Smad2/3
de-phosphorylation and thus termination of TGF-β/R-Smad signaling. Studies will also
be performed to examine MALAT1 interaction with the H3K36 methyltransferase SETD2
and other chromatin-modifying proteins. In Specific Aim 2, we will assess the
therapeutic efficacy of inhibiting MALAT1 for HCC treatment in preclinical models. The
proposed studies will further define the molecular mechanisms of hepatic
carcinogenesis and provide important implication for development of novel target
therapies.

## Key facts

- **NIH application ID:** 9832648
- **Project number:** 5R01CA226281-02
- **Recipient organization:** TULANE UNIVERSITY OF LOUISIANA
- **Principal Investigator:** Tong Wu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $347,034
- **Award type:** 5
- **Project period:** 2018-12-06 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9832648

## Citation

> US National Institutes of Health, RePORTER application 9832648, The Long Noncoding RNA MALAT1 in Liver Cancer (5R01CA226281-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9832648. Licensed CC0.

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