ArticleFrontiers in bioengineering and biotechnology2020
3'-UTR Shortening Contributes to Subtype-Specific Cancer Growth by Breaking Stable ceRNA Crosstalk of Housekeeping Genes.
Article in Frontiers in bioengineering and biotechnology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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7 citing papers in PubMed, 12 citations in OpenAlex.
- Quantitative measures to assess the quality of cellular indexing of transcriptomes and epitopes by sequencing data.Frontiers in bioinformatics · 2025Article
- Dichotomous intronic polyadenylation profiles reveal multifaceted gene functions in the pan-cancer transcriptome.Experimental & molecular medicine · 2024Article
- The Mechanisms of miRNAs on Target Regulation and their Recent Advances in Atherosclerosis.Current medicinal chemistry · 2024Review
- Alternative polyadenylation regulation in cardiac development and cardiovascular disease.Cardiovascular research · 2023Review
- Deep neural networks with knockoff features identify nonlinear causal relations and estimate effect sizes in complex biological systems.GigaScience · 2022Article
- The Estrogen Receptor α Signaling Pathway Controls Alternative Splicing in the Absence of Ligands in Breast Cancer Cells.Cancers · 2021Article
- Transforming growth factor‑β1 functions as a competitive endogenous RNA that ameliorates intracranial hemorrhage injury by sponging microRNA‑93‑5p.Molecular medicine reports · 2021Article
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Shortening of 3'UTRs (3'US) through alternative polyadenylation is a post-transcriptional mechanism that regulates the expression of hundreds of genes in human cancers. In breast cancer, different subtypes of tumor samples, such as estrogen receptor positive and negative (ER+ and ER-), are characterized by distinct molecular mechanisms, suggesting possible differences in the post-transcriptional regulation between the subtype tumors. In this study, based on the profound tumorigenic role of 3'US interacting with competing-endogenous RNA (ceRNA) network (3'US-ceRNA effect), we hypothesize that the 3'US-ceRNA effect drives subtype-specific tumor growth. However, we found that the subtypes are available in different sample sizes, biasing the ceRNA network size and disabling the fair comparison of the 3'US-ceRNA effect. Using normalized Laplacian matrix eigenvalue distribution, we addressed this bias and built tumor ceRNA networks comparable between the subtypes. Based on the comparison, we identified a novel role of housekeeping (HK) genes as stable and strong miRNA sponges (sponge HK genes) that synchronize the ceRNA networks of normal samples (adjacent to ER+ and ER- tumor samples). We further found that distinct 3'US events in the ER- tumor break the stable sponge effect of HK genes in a subtype-specific fashion, especially in association with the aggressive and metastatic phenotypes. Knockdown of NUDT21 further suggested the role of 3'US-ceRNA effect in repressing HK genes for tumor growth. In this study, we identified 3'US-ceRNA effect on the sponge HK genes for subtype-specific growth of ER- tumors.
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