A snapshot of the role of estrogen-regulated divergent non-coding transcripts

Abstract

Recent high-throughput sequencing technologies have discovered various polymerase II transcribed transcripts. The majority of them are non-protein-coding, understudied and poorly conserved. Non-coding transcripts are categorised based on their location in the genome and the direction in which they are transcribed; these categories classify a non-coding transcript as either antisense, intergenic or divergent. The RNAs belonging to divergent classes consist of two transcripts, transcribed in sense and antisense direction, generated from the same promoter or locus. Multiple environmental and genetic cues can determine the regulation of these transcripts. One of the well-known signalling molecules, estrogen, has been shown to play a vital role in the activation and regulation of divergent transcripts by mediating effects through the estrogen receptors. Emerging studies have shown a strong causative effect between estrogen-regulated divergent transcripts and diseases such as cancer. However, few, viz., lncRNA67, CUPID1 and CUPID2, show a causal relationship with estrogen-dependent biology. This mini-review summarises their role in estrogen-dependent processes that may drive the research to identify novel estrogen-signalling regulators.

Keywords

breast cancer / cancer / estrogen / long non-coding RNAs / signalling

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2025 The Author(s). Clinical and Translational Discovery published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.