# Non-Coding RNA: Architects of Cellular Complexity and Agents of Malignancy

## TL;DR

Non-coding RNAs regulate gene expression and contribute to cancer by altering cellular regulatory networks.

## Contribution

The paper proposes that ncRNA alterations drive the transition to cancer by changing the epigenetic landscape.

## Key findings

- ncRNAs form a dynamic genome-wide regulatory network that controls gene expression.
- Cancer arises as a neoplastic attractor state due to ncRNA dysregulation and subsequent genetic mutations.
- ncRNAs act as key regulators in cellular processes and transitions between cell states.

## Abstract

Non-coding RNAs (ncRNAs) are conserved in the genome of cells across the three domains of life. They comprise a diverse group that are particularly prominent in metazoans where they provide a crucial interface between genes and proteins, participating in key cellular processes at different levels: from control of DNA transcription to modulation of messenger RNA stability to modification of protein activity. The interactions of ncRNAs with one another as well as with other RNAs, DNA and proteins form the basis of a genome-wide regulatory network (GRN). Because of the mutual influence of its components on each other, the GRN is a dynamic system. Further, the GRN imposes constraints on which genes are expressed and when, leading to specific gene-expression patterns or transcriptomes. The configurations of the activities of all gene loci represent self-stabilizing cell states, referred to as “attractor” states, each of which corresponds to a distinct cell type. The cancer cell is also an attractor state that arises from a change in the topography of the epigenetic landscape caused by dysregulation of the GRN. It is proposed that the transition to a neoplastic attractor state is caused by ncRNA alterations, while subsequent somatic mutations of oncogenes and tumor suppressor genes drive cell proliferation and clonal expansion.