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Novel 7SK non-coding RNA fusions in soft tissue sarcomas to tumorigenesis

软组织肉瘤中新型 7SK 非编码 RNA 融合与肿瘤发生

基本信息

批准号：
10361508
负责人：
Joyce Ellen Ohm
金额：
$ 8.41万
依托单位：
ROSWELL PARK CANCER INSTITUTE CORP
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-03-01 至 2023-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10361508
关键词：
Address Biological Process Biology Cell Cycle Cell Cycle Regulation Cell Line Cells Characteristics Chromosomal Rearrangement Data Diagnostic Disease Disease Progression Elongation Factor Engineering Foundations Fusion Oncogene Proteins Future Gene Expression Gene Expression Profile Genetic Transcription Grant Histologic In Situ Hybridization Knowledge Link Malignant Neoplasms Manuscripts Mesenchymal Mesenchymal Cell Neoplasm Molecular Normal Cell Normal tissue morphology Oncogenic Pathogenesis Patients Prevalence Primary Neoplasm Proteins RNA RNA Polymerase III RNA Splicing RNAse MRP RNase P Role Sampling Signal Transduction Small Nuclear RNA Small RNA Soft tissue sarcoma Structure Tissue Microarray Transcript Transcriptional Regulation Translations Tumor Subtype Tumor Tissue Untranslated RNA Work base cancer cell cancer type cohort design experimental study fusion gene genetic signature malignant phenotype novel rare cancer sarcoma transcriptome sequencing tumor tumor growth tumorigenesis

项目摘要

PROJECT SUMMARY Soft tissue sarcomas (STS) are rare tumors of mesenchymal origin that are often characterized by diagnostic fusion oncoproteins corresponding with tumor subtype. We have recently observed that STS also harbor a significant number of non-coding RNA (ncRNA) fusions, with RN7SK (7SK) fusions being the most prominent. 7SK ncRNA fusions predominantly involve other RNA polymerase III transcripts, occur at specific 7SK breakpoints which reflect known characteristics of secondary structure, and are enriched in primary tumors over cell lines. Furthermore, the presence of 7SK fusions is associated with a unique gene expression signature, independent of tumor subtype. This gene signature involves altered expression of transcriptional networks linked to transcriptional regulation, splicing, and translation, known functions of 7SK and its fusion partners. Along with the predicted secondary structure of ncRNA fusions, this suggests the potential for significant disruption of normal 7SK regulatory function in these tumors. Our overall hypothesis is that 7SK ncRNA fusions represent a common mechanism by which normal transcription regulation is disrupted in soft tissue sarcomas, contributing to disease pathogenesis. This R03 grant has been designed to allow us to gather essential preliminary data to understand the biological function of these ncRNA in STS and query the prevalence of these ncRNA fusions in other tumor types. Two specific aims are proposed: • Specific Aim 1: To determine effects of 7SK fusions on gene expression and tumor growth • Specific Aim 2: To characterize the prevalence of ncRNA fusions in STS and normal mesenchymal cells and to extend these findings to other types of cancer and their normal counterparts If successful, this study will lay a foundation for future work focused on understanding the biology of ncRNA fusions in tumorigenesis.

项目总结