The role of small RNA modifications in glioma

小RNA修饰在神经胶质瘤中的作用

• 批准号: 10590764
• 负责人: Zhangli Su
• 金额: $ 11.06万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-03-11 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10590764
• 关键词: Address; Affect; Area; Base Pairing; Benchmarking; Biochemistry; Biogenesis; Bioinformatics; Biological Process; Biology; CRISPR screen; Cancer Biology; Cell Line; Cell Proliferation; Cells; Chemotherapy and/or radiation; Classification; Data; Data Set; Development; Disease Management; Ensure; Environment; Epigenetic Process; Family; Gene Expression; Gene Silencing; Genomics; Glioblastoma; Glioma; Goals; Interruption; Investigation; Learning; Malignant Neoplasms; Malignant neoplasm of brain; Manuscripts; Mentors; MicroRNAs; Mining; Modification; Molecular Biology; Mus; Operative Surgical Procedures; Outcome; Pathogenesis; Pathway interactions; Patients; Persons; Phase; Phenotype; Play; Positioning Attribute; Preparation; Primary Brain Neoplasms; Process; RNA; Recurrence; Regulation; Regulator Genes; Research; Role; Sampling; Shapes; Site; Small RNA; Techniques; Testing; The Cancer Genome Atlas; Training; Transfer RNA; Universities; Untranslated RNA; Virginia; Xenograft Model; Xenograft procedure; base; bioinformatics tool; cancer type; common treatment; effective therapy; experimental study; genomic tools; improved; in vivo; innovation; insight; mortality; new therapeutic target; novel; overexpression; posttranscriptional; prognostic; skills; stem-like cell; therapeutic target; tool; transcriptome; transcriptome sequencing; tumor

PROJECT SUMMARY/ABSTRACT Background: Small non-coding RNAs including microRNAs and tRNA-related fragments (tRFs) are important regulators of global gene expression and have been shown to play key roles in normal development. Recent evidence suggests small RNAs (especially tRFs) can be regulated via modifications, however global analysis of small RNA modifications in cancers is still lacking due to lack of tools. In this proposal I will test whether dysregulation of small RNA modifications play a role in cancer biology. I will focus on glioma/glioblastoma (GBM), vicious cancer types that are barely treatable. Research: The candidate's preliminary results indicate that tRFs are novel regulators of gene expression and cell phenotypes in gliomas and their activity could be regulated by small RNA modification status. The candidate already detected such small RNA modifications in GBM and GSC (glioma stem-like cells) cell lines and also GBM patients. This proposal aims to understand the biological functions of these newly identified small RNA modifications and tRFs in gliomas. If completed, this will bring novel insights to the field and be a perfect niche to launch an independent lab. Three aims are proposed, each based on preliminary data, and taking into the independent phase. Aim 1 will determine the glioma-relevant small RNA modification factors. Aim 2 will define the functional roles and targetome of glioma-prognostic tRFs. Aim 3 will elucidate novel RBP- based mechanisms of small RNA modification regulating tRF targetome and pathways in gliomas. GSC cultures and mouse xenografts, genomics and bioinformatics will be employed to tackle these questions. The proposed research plan will reveal a novel gene regulatory mechanism by small RNA modifications and identify potential therapeutic targets for glioma treatment. Candidate: The candidate's long-term goal is to utilize her background in biochemistry, small RNA and molecular biology to understand new gene regulatory mechanism in cancer biology. She already processes a lot of the skills needed to conduct proposed experiments, however she is in great need to obtain additional training in glioma biology in order to further test her hypothesis (with co-mentor who is an expert in GBM field). The K99 mentored phase will allow her to build on her current data, expand on several new areas, and learn new techniques to launch her own lab. A mentoring committee of 6 is proposed to ensure the candidate get guidance to help her achieve independence. Environment: The proposed project will be conducted at University of Virginia, which has an outstanding environment for the proposed training and research.

项目总结/文摘