# A novel lncRNA-responsive and xenobiotic receptor-mediated regulation of drug metabolism and disposition

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2021 · $357,994

## Abstract

A novel lncRNA-responsive and xenobiotic receptor-mediated regulation of drug metabolism and
disposition
Abstract
Drug metabolism and disposition are essential xenobiotic responses. The long non-coding RNAs (lncRNAs)
are non-coding RNAs larger than 200 nucleotides (nt) in length and do not have protein-coding potentials.
Although many of the biological functions of lncRNAs have been recognized, it is unclear whether and how
lncRNAs can regulate the expression of drug-metabolizing enzymes and transporters and if so, whether the
regulations are implicated in cancer chemo-resistance. Through integrative analysis of cancer non-coding
genomic and high-through drug screening data of 505 cancer cell lines, our preliminary study have discovered
and functionally characterized a group of ADME(drug absorption, distribution, metabolism, and excretion)
chemo-resistance lncRNAs, including LINC00992, whose up-regulation is associated with resistance to more
than 100 chemotherapy compounds and may regulate drug-metabolizing enzymes and transporters through
interacting with xenobiotic nuclear receptor. We hypothesize that dysregulation of ADME chemo-resistance
lncRNAs is an important contributor for the development of cancer chemo-resistance. Mechanistically, ADME
chemo-resistance lncRNAs affect chemo-resistance through their regulation of drug-metabolizing enzymes and
transporters that are responsible for the metabolism and disposition of chemotherapy drugs. We propose three
specific aims to test our hypotheses: In Aim 1, we will perform bioinformatic analysis and molecularly clone of
lncRNAs associated with cancer chemo-resistance and clinical prognosis. In Aim 2: we will functional
characterize of ADME chemo-resistance lncRNAs, including LINC00992, using in vivo and in vitro cancer
chemotherapy models. In Aim 3: we will determine the mechanism by which ADME chemo-resistance
lncRNAs, including LINC00992, regulate the expression of drug-metabolizing enzymes and transporters.
Chemotherapy remains a mainstay in the clinical management of cancer patients, but chemo-resistance is a
major challenge to overcome. Understanding the novel lncRNA responsive and xenobiotic nuclear receptor-
mediated chemo-resistance will help provide novel strategies to enhance therapeutic efficacy and avoid the
development of chemo-resistance.

## Key facts

- **NIH application ID:** 10096096
- **Project number:** 1R01CA255196-01
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Da Yang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $357,994
- **Award type:** 1
- **Project period:** 2020-12-01 → 2025-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10096096

## Citation

> US National Institutes of Health, RePORTER application 10096096, A novel lncRNA-responsive and xenobiotic receptor-mediated regulation of drug metabolism and disposition (1R01CA255196-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10096096. Licensed CC0.

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