Role of lncRNA-Encoded Peptides Involved in Kidney Cancer
Abstract
Increasing evidence suggests that a number of long non-coding RNAs (lncRNAs) can encode small size peptides, i.e., micropeptides, and, moreover, some of the micropeptides have been shown to play a role in normal cell functions or disease processes. These micropeptides are historically ignored in gene annotation studies simply because they are small, thus, the function of the vast majority of such micropeptides is not known. In particular, it is not clear whether they can play any role in kidney cancer. Our proposed study aims to systematically identify lncRNA-encoded micropeptides important to hypoxia signaling pathway in kidney cancer because hypoxia factors regulate a number of genes involved in cell survival, resistance to chemo- and radiotherapy, and are associated with poor prognosis in kidney cancer patients. Therefore, we hypothesize that lncRNA-encoded micropeptides can play a role in the hypoxia signaling pathway in kidney cancer. To test this hypothesis, we will generate a CRISPR sgRNA library against potential lncRNA-encoded micropeptides and perform functional screening. To functionally identify such sgRNAs from the library we will also generate a hypoxia response element (HRE) reporter that would enable us to identify both positive and negative sgRNA clones for hypoxia pathway by selection of the sgRNA library against blastincidine or ganciclovir. Finally, we will perform functional characterization of candidate lncRNA-encoded micropeptides corresponding to the sgRNA clones by manipulating their expression through knockout/rescue or ectopic expression to determine the effect of such manipulations on the hypoxia signaling pathway. We expect that identification of such lncRNA-encoded micropeptides will provide new insight into kidney cancer biology, and these peptides may serve as novel biomarkers or therapeutic targets.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110861
Entities
People
- Yin-Yuan Mo
Organizations
- United States Army
- University of Mississippi Medical Center