Colorectal cancer (CRC) accounts for 10 per cent of all cancer related deaths worldwide, and New Zealand has some of the highest incidence rates globally. Currently available targeted therapies are largely based on modulating protein function, however, only 1–2 per cent of the human genome is protein coding. Long non-coding RNAs (lncRNAs) are ribonucleic acid transcripts – 200 nucleotides that do not code for a protein. Around 100,000 lncRNA genes exist in the human genome, however, the molecular function of most lncRNAs remains unknown. The lncRNA human Mammary Tumour Associated RNA 17 (hMaTAR17) is overexpressed in several different cancer types, including breast, lung, and colorectal. The shared overexpression is unusual for a lncRNA, as most are expressed in a cell- and cancer-type specific manner. In our previous studies, hMaTAR17 loss-of-function models showed reduced tumour cell proliferation, invasion and organoid branching in breast cancer, which suggests that hMaTAR17 likely plays an important role in tumour progression. We hypothesise that hMaTAR17 also acts to modulate cancer related genes and pathways to impact colorectal cancer (CRC) progression. We developed a CRISPR/Cas9 knockout and CRISPRi knockdown of hMaTAR17 in HCT-116 cells to investigate phenotypic changes upon hMaTAR17 loss-of-function in CRC. We performed cell characterisation assays, and identified a significant decrease in proliferation and migration of the hMaTAR17 knockout cells compared to control cells. RNA-Sequencing revealed a number of gene expression changes upon hMaTAR17 loss, including significantly reduced expression of vimentin, potentially implicating hMaTAR17 in epithelial-mesenchymal transition. RNA-FISH experiments showed that hMaTAR17 localizes to the cytoplasm, and protein interaction studies revealed that hMaTAR17 is implicated with cancer and growth related proteins including lamin. Together, these results indicate that hMaTAR17 may serve as a potential new drug target for metastatic colorectal cancer.
|Date||Tuesday, 7 December 2021|
|Time||12:00pm - 1:00pm|
|Audience||Public,Undergraduate students,Postgraduate students,Staff|
|Event Category||Health Sciences|
|Location||Biochemistry Seminar Room G.13 (BIG13), Dunedin|
|Contact Name||Department of Biochemistry|