Investigating the oncogenic role of LINC00673 in colorectal cancer
Primary Supervisor: Professor Ian Tomlinson
Second Supervisor: Dr Shamir Montazid
Project Overview
Long non-coding RNAs (lncRNAs) have emerged as critical regulators of gene expression in tumorigenesis. Recent work from our group has demonstrated that overexpression of LINC00673 (aka LINC00511) in both human and murine colorectal cancer (CRC) cell lines induces profound transcriptional changes in key CRC pathways. However, the in vivo relevance of these findings remains unexplored.
This project aims to investigate the oncogenic roles of LINC00673 in intestinal epithelium using a novel transgenic mouse model. A TetON-inducible construct expressing human LINC00673 will be integrated into the murine genome and activated specifically in the intestinal epithelium. Transcriptomic profiling of intestinal tissues will be performed to identify global gene expression alterations upon LINC00673 induction. Key candidate targets and pathways will be validated using histology, qPCR, cell lines, and intestinal organoid assays.
The mouse transcriptomic data will be cross-compared with human CRC datasets from the 100,000 Genomes Project and TCGA to identify conserved LINC00673-associated gene signatures and clinical correlations. Finally, pathway perturbations will be performed in CRC organoids using small molecules to identify therapeutic targets.
This integrative study will elucidate how LINC00673 reprograms intestinal epithelial gene expression and contributes to colorectal tumorigenesis, providing novel mechanistic insights and potential therapeutic targets.
Training Opportunities
The student will receive advanced training in molecular and cancer biology, mouse transgenesis, transcriptomic data analysis, and computational genomics. Laboratory skills will include cloning, transgenic model validation, RNA sequencing, qPCR, histology, and organoid culture. Bioinformatics training will cover RNA-seq data processing, pathway enrichment, and cross-species comparative analyses using TCGA and 100k Genomes data.
The student will benefit from the Tomlinson Lab’s expertise in colorectal cancer genetics and access to the Department of Oncology’s state-of-the-art facilities. The project offers an excellent platform for developing dry and wet-lab skills at the interface of cancer biology, functional genomics, and translational research.
References
Feng, L.M., Zhao, D.W., Li, S.J. and Huang, J., 2018. Association of the upregulation of LncRNA00673 with poor prognosis for colorectal cancer. European Review for Medical & Pharmacological Sciences, 22(3). https://www.europeanreview.org/wp/wp-content/uploads/687-694.pdf
Li, J., Li, Y., Meng, F., Fu, L. and Kong, C., 2018. Knockdown of long non-coding RNA linc00511 suppresses proliferation and promotes apoptosis of bladder cancer cells via suppressing Wnt/β-catenin signaling pathway. Bioscience reports, 38(4), p.BSR20171701. https://pubmed.ncbi.nlm.nih.gov/30042171/
Hu, Y., Zhang, Y., Ding, M. and Xu, R., 2021. Lncrna linc00511 acts as an oncogene in colorectal cancer via sponging mir-29c-3p to upregulate nfia. OncoTargets and therapy, pp.13413-13424. https://pubmed.ncbi.nlm.nih.gov/33536761/