The 3' end of the tale-neglected isoforms in cancer.

The evolutionary expansion of 3' untranslated regions (3'UTRs), along with the incorporation of transposable elements and alternative polyadenylation (APA) sites, has introduced additional layers of gene expression control in eukaryotes. Consequently, 3'UTRs regulate the stability, translation, and localization of mRNAs by interacting with RNA-binding proteins and non-coding RNAs, thereby contributing to cell-type-specific and context-dependent gene expression. Mounting evidence highlights the importance of non-coding regions, particularly 3'UTRs, in normal physiology and disease states, including cancer.

3'UTR RNA editing driven by ADAR1 modulates MDM2 expression in breast cancer cells.

Epitranscriptomic changes in the transcripts of cancer related genes could modulate protein levels. RNA editing, particularly A-to-I(G) editing catalyzed by ADAR1, has been implicated in cancer progression. RNA editing events in the 3' untranslated region (3'UTR) can regulate mRNA stability, localization, and translation, underscoring the importance of exploring their impact in cancer.

Differential expression of mRNA 3'-end isoforms in cervical and ovarian cancers.

Early diagnosis and therapeutic targeting are continuing challenges for gynecological cancers. Here, we focus on cancer transcriptomes and describe the differential expression of 3'UTR isoforms in patients using an algorithm to detect differential poly(A) site usage. We find primarily 3'UTR shortening cases in cervical cancers compared with the normal cervix.

An alternatively spliced PD-L1 isoform PD-L1∆3, and PD-L2 expression in breast cancers: implications for eligibility scoring and immunotherapy response.

Targeting PD-1/PD-L1 has shown substantial therapeutic response and unprecedented long-term durable responses in the clinic. However, several challenges persist, encompassing the prediction of treatment effectiveness and patient responses, the emergence of treatment resistance, and the necessity for additional biomarkers. Consequently, we comprehensively explored the often-overlooked isoforms of crucial immunotherapy players, leveraging transcriptomic analysis, structural modeling, and immunohistochemistry (IHC) data.

Identification of an mRNA isoform switch for HNRNPA1 in breast cancers.

Roles of HNRNPA1 are beginning to emerge in cancers; however, mechanisms causing deregulation of HNRNPA1 function remain elusive. Here, we describe an isoform switch between the 3'-UTR isoforms of HNRNPA1 in breast cancers. We show that the dominantly expressed isoform in mammary tissue has a short half-life.

EGF-SNX3-EGFR axis drives tumor progression and metastasis in triple-negative breast cancers.

Epidermal growth factor receptor (EGFR) has critical roles in epithelial cell physiology. Over-expression and over-activation of EGFR have been implicated in diverse cancers, including triple-negative breast cancers (TNBCs), prompting anti-EGFR therapies. Therefore, developing potent therapies and addressing the inevitable drug resistance mechanisms necessitates deciphering of EGFR related networks.