# Profound alterations of cancer transcriptomes by the RNase L inhibitor ABCE1 through the modulation of UU/UA-dinucleotide rich transcript abundance

## TL;DR

This study shows that overexpression of the protein ABCE1 in cancer cells significantly changes the types of RNA present, affecting cell growth and patient survival in colorectal and lung cancer.

## Contribution

The study reveals that ABCE1 overexpression modulates UU/UA-rich transcript abundance, linking it to altered cancer cell behavior and patient outcomes.

## Key findings

- ABCE1 overexpression is strongly associated with upregulation of UU/UA-rich transcripts and downregulation of UU/UA-poor ones in colorectal cancer.
- High ABCE1 levels correlate with improved survival in colorectal cancer, possibly due to immune response activation.
- Knockdown of ABCE1 in CRC cell lines reduces proliferation.

## Abstract

Tumorigenesis is commonly driven by genetic mutations and disruptions in cellular signalling pathways. Here we show that the oncogenic overexpression of the RNase L inhibitor ABCE1, a component of interferon signalling, leads to distinct and extensive deviations in cancer transcriptomes. RNase L is a cellular endonuclease that cleaves RNA molecules at specific UU and UA dinucleotide sites. Typically, it is activated by viral infections and interferon signalling leading to targeting and destruction of UU/UA-rich viral and cellular mRNA. RNase L has also homoeostatic and tumour suppressive roles. Relying on patient transcriptomic data, we show that ABCE1 is extensively overexpressed in colorectal cancer (CRC) and to a lesser extent in lung cancer. This upregulation was strongly associated with the co-upregulation of almost all UU/UA rich transcripts and downregulation of those that are UU/UA-poor. Many of upregulated mRNAs code for proteins involved in cell cycle regulation and mitosis. Accordingly, the knockdown of ABCE1 in the CRC cell line HT29 led to reduced proliferation. Surprisingly, the very high ABCE1 levels were associated with improved patient survival in CRC. This observation might be related to an anti-ABCE1-specific immune response due to the induction of tumour-reactive cytotoxic T lymphocytes by ABCE1 as previously reported. In lung cancer ABCE1 overexpression is milder and is associated with poor survival. We report a measurable, specific, and extensive modulation of cancer transcriptomes by the oncogenic overexpression of a component of interferon signalling with unexpected outcomes on patient survival.