Lin28A and Lin28B Inhibit let-7 MicroRNA Biogenesis by Distinct Mechanisms

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Lin28A and Lin28B Inhibit let-7 MicroRNA Biogenesis by Distinct Mechanisms

Lin28A and Lin28B selectively block the expression of let-7 microRNAs and function as oncogenes in a variety of human cancers. Lin28A recruits a TUTase (Zcchc11/TUT4) to let-7 precursors to block processing by Dicer in the cell cytoplasm. Here we find that unlike Lin28A, Lin28B represses let-7 processing through a Zcchc11-independent mechanism. Lin28B functions in the nucleus by sequestering pr...

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The precise control of microRNA (miRNA) biosynthesis is crucial for gene regulation. Lin28A and Lin28B are selective inhibitors of biogenesis of let-7 miRNAs involved in development and tumorigenesis. Lin28A selectively inhibits let-7 biogenesis through cytoplasmic uridylation of precursor let-7 by TUT4 terminal uridyl transferase and subsequent degradation by Dis3l2 exonuclease. However, a rol...

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miR-203 enhances let-7 biogenesis by targeting LIN28B to suppress tumor growth in lung cancer

Human cancers often exhibit increased microRNA (miRNA) biogenesis and global aberrant expression of miRNAs; thus, targeting the miRNA biogenesis pathway represents a novel strategy for cancer therapy. Here, we report that miR-203 enhances the biogenesis of tumor suppressor let-7 in lung cancer by directly targeting LIN28B. Specially, we found that the LIN28B protein levels were dramatically inc...

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The Hippo pathway effectors TAZ/YAP regulate dicer expression and microRNA biogenesis through Let-7.

MicroRNAs (miRNAs) are genome-encoded small double-stranded RNAs that have emerged as key regulators of gene expression and are implicated in most aspects of human development and disease. Canonical miRNA biogenesis involves processing of ∼70-nucleotide pre-miRNA hairpins by Dicer to generate mature ∼22-nucleotide miRNAs, which target complementary RNA sequences. Despite the importance of miRNA...

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Lethal-7 (let-7) microRNA (miRNA) serves a pivotal role in a number of physiological processes and is associated with the occurrence and development of multiple disorders such as cancer. The present study aimed to use a newly developed stem‑loop strategy for reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) to distinguish let‑7 miRNA family members that differ by as little ...

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ژورنال

عنوان ژورنال: Cell

سال: 2011

ISSN: 0092-8674

DOI: 10.1016/j.cell.2011.10.039