We are on the brink of a paradigm shift in both theoretical and clinical oncology. Genomic and transcriptomic profiling, alongside personalized approaches that account for individual patient variability, are increasingly shaping discourse. Discussions on the future of personalized cancer medicine are mainly dominated by the potential of non-coding RNAs (ncRNAs), which play a prominent role in cancer progression and metastasis formation by regulating the expression of oncogenic or tumor suppressor proteins at transcriptional and post-transcriptional levels; furthermore, their cell-free counterparts might be involved in intercellular communication. Non-coding RNAs are considered to be promising biomarker candidates for early diagnosis of cancer as well as potential therapeutic agents. This review aims to provide clarity amidst the vast body of literature by focusing on diverse species of ncRNAs, exploring the structure, origin, function, and potential clinical applications of miRNAs, siRNAs, lncRNAs, circRNAs, snRNAs, snoRNAs, eRNAs, paRNAs, YRNAs, vtRNAs, and piRNAs. We discuss molecular methods used for their detection or functional studies both in vitro and in vivo. We also address the challenges that must be overcome to enter a new era of cancer diagnosis and therapy that will reshape the future of oncology.

Xenoestrogens are synthetic or natural compounds that mimic the effect of endogenous estrogens by binding to estrogen receptors (ERs). Human exposure to xenoestrogens is increasing globally, raising substantial concerns regarding their endocrine-disrupting effects. Here, we investigated the ERα-mediated genomic and transcriptional response of human ovarian cells following exposure to estradiol (E2), zearalenone (ZEA), and bisphenol A (BPA) using ChIP-seq integrated with transcriptomic analysis. Our results demonstrate that the ERα-dependent response induced by ZEA closely resembles that of E2, whereas BPA elicits a markedly attenuated response. ERα signal intensity was higher in cells treated with E2 or ZEA than in cells treated with BPA, indicating reduced ERα occupancy in response to BPA exposure. We identified 641 genomic regions that were occupied by ERα after any treatment, defining a core set of shared binding sites. Integration with mRNA-seq datasets revealed 162 ERα-binding sites located within ±50 kb of the transcription start sites of 109 upregulated genes. Among these, 28 genes were induced across all treatments, constituting a core estrogen-responsive gene set in human ovarian cells. RT-qPCR validation of six representative genes (GREB1, RASGRP1, CISH, RBBP8, KCNF1, and LONRF2) confirmed stronger and sustained transcriptional induction following E2 and ZEA exposure than following BPA exposure; this induction was inhibited by the ERα antagonist MPP. Our findings suggest that BPA has a lower capacity to activate ERα chromatin binding and downstream transcriptional programs, affecting primarily high-affinity estrogen-responsive loci in human ovarian cells.