{"doi":"10.3389/fbioe.2020.00334","title":"3′-UTR Shortening Contributes to Subtype-Specific Cancer Growth by Breaking Stable ceRNA Crosstalk of Housekeeping Genes","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.","journal":"Frontiers in Bioengineering and Biotechnology","year":2020,"id":86874,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":12,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9487,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":409930,"name":"Soyeon Kim","orcid":"0000-0003-1573-2733","position":1,"is_corresponding":false},{"id":409931,"name":"Yulong Bai","orcid":"0000-0002-9365-3742","position":2,"is_corresponding":false},{"id":247568,"name":"Brenda Diergaarde","orcid":"0000-0002-3578-6547","position":3,"is_corresponding":false},{"id":409933,"name":"Hyun Jung Park","orcid":"0000-0002-8324-2624","position":4,"is_corresponding":false},{"id":409932,"name":"Zhenjiang Fan","orcid":"0000-0002-5889-5340","position":0,"is_corresponding":true}],"reference_count":70,"raw_metadata":null,"created_at":"2026-07-18T21:59:03.706190Z","pmid":"32411683","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}