# Systematic Characterization of Small Nucleolar RNAs in Cancer

> **NIH NIH R01** · TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR · 2021 · $406,018

## Abstract

Abstract
Despite recent advancements in treatment options for cancer, a majority of cancer types continue to lack fully
characterized and effective targeted therapies. This insufficiency has resulted in the demand for alternative,
previously unconsidered treatment approaches to improve disease diagnostics, prognoses, and patient
survival outcomes. Recently, we performed integrative analysis for small nucleolar RNA (snoRNAs) in a large
number of patient samples and identified 46 snoRNAs that exhibit broad-spectrum clinical significance with 12
or more types of cancer. We developed a data portal, snoRNA in cancers (SNORic), which allows researchers
to explore the significance of individual snoRNAs in cancer. SNORic has been accessed >100,000 times since
its release in 2017, suggesting its broad impact in the biomedical research community. We provided initial
genetic evidence indicating that elevated expression of snoRNAs facilitated the tumorigenesis of mammary
gland malignancies. Mechanistically we demonstrated that SNORD46 plays important roles in promoting the
initiation, growth, invasion and progression of TNBC. Therefore, elucidation of the roles of snoRNAs in
promoting tumorigenesis serves as the first step in the development of a novel class of snoRNA-based
biomarkers and therapeutic targets.
 Our central hypothesis is that snoRNAs serve as essential RNA targets in promoting cancer initiation,
progression, and drug resistance, which could be attenuated in vivo by an antisense oligonucleotide-based
targeted therapy. In specific aim 1, we will delineate the diagnostic and prognostic values of these snoRNAs in
triple-negative breast cancer (Aim 1.1). We will demonstrate the molecular mechanism that these snoRNAs
promote TNBC cell proliferation, mobility and invasion (Aim 1.2). We will demonstrate that antisense
oligonucleotide-based snoRNA targeted therapy effectively inhibits TNBC growth in vivo (Aim 1.3). We will
evaluate and interpret causal effects through molQTL analysis (Aim 1.4). In specific aim 2, we will determine
the role of three snoRNAs in breast cancer drug resistance (Aim 2.1). We will understand the molecular
mechanisms for drug resistance through multi-omics data (Aim 2.2). To expand our perspective on drug
resistance, we will predict the drug response from individual snoRNA expression with the augmentation of
deep learning (Aim 2.3). We will study the drug responses effects among snoRNA-based subtypes (Aim 2.4).
We will build a user-friendly data portal for releasing the date generated through integrative analysis (Aim 2.5).
This study will significantly advance the prognostic, diagnostic, and therapeutic potential of snoRNAs; the
absence of this research work will greatly hinder the realization of snoRNA-based therapeutic considerations
for cancer patients.

## Key facts

- **NIH application ID:** 10277525
- **Project number:** 1R01CA262623-01
- **Recipient organization:** TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR
- **Principal Investigator:** Leng Han
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $406,018
- **Award type:** 1
- **Project period:** 2021-09-22 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10277525

## Citation

> US National Institutes of Health, RePORTER application 10277525, Systematic Characterization of Small Nucleolar RNAs in Cancer (1R01CA262623-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10277525. Licensed CC0.

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