Investigating RNA Isoform Diversity in Colorectal Cancer at Single-Cell Level

Ping Lu from Peking University in China presented at London Calling 2024 on “Full-length RNA isoforms in human colorectal cancer at single-cell resolution.” Lu said colorectal cancer is the third most common cancer worldwide and the second leading cause of cancer death! Lu also mentioned that single-cell resolution is now necessary to better understand the diversity and complexity of the human transcriptome. Lu shared examples of how different isoforms can have very different functions. The aim of their study was to learn about the characteristics of RNA isoforms in colorectal cancer. Nine samples were obtained from patients for deep nanopore sequencing of single-cell transcripts and exomes. Lu and team quantified expression in healthy and cancer samples. They learned that cancer cells had mutant alleles and were enriched in oncogenic functions. Alternative splicing events were identified. The team is interested in differential transcript usage in cancer cells. Differential transcript usage (DTU) in colorectal cancer cells was evaluated. Cancer cells switch the major cMyc isoform from cMyc1 to cMyc2. Lu summarized the findings by stating that “high-depth long-read scRNA seq on epithelium of CRC tumor and normal research samples from 9 patients” helped reveal mutant allele-dominant expression patterns and increased complexity in transport diversity. Importantly, this work revealed “substantial shifts in isoform usage that result in alterations of protein sequences with distinct carcinogenic effects.”

How does isoform usage differ in colorectal cancer cells? AI-generated image.