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• W2934446930 abstract "ABSTRACT Shortening of 3′UTRs (3′US) through alternative polyadenylation (APA) is a post-transcriptional mechanism that regulate 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 size, 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 the 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, a master 3′-UTR regulator in HeLa cells, confirmed the causal role of 3′US-ceRNA effect 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." @default.
• W2934446930 created "2019-04-11" @default.
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• W2934446930 date "2019-04-07" @default.
• W2934446930 modified "2023-10-14" @default.
• W2934446930 title "3′-UTR shortening contributes to subtype-specific cancer growth by breaking stable ceRNA crosstalk of housekeeping genes" @default.
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• W2934446930 doi "https://doi.org/10.1101/601526" @default.
• W2934446930 hasPublicationYear "2019" @default.
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