The Imprinted H19 LncRNA Antagonizes Let-7 MicroRNAs

By Amanda N. Kallen, Xiao-Bo Zhou, Jie Xu, Chong Qiao, Jing Ma, Lei Yan, Lingeng Lu, Chaochun Liu, J. Yi, Haifeng Zhang and 5 more. Molecules and Cells, 2013

1,037 citations recorded by the source corpus.

SUMMARY Abundantly expressed in fetal tissues and adult muscle, the developmentally regulated H19 long noncoding RNA (lncRNA) has been implicated in human genetic disorders and cancer. However, how H19 acts to regulate gene function has remained enigmatic, despite the recent implication of its encoded miR675 in limiting placental growth. We noted that vertebrate H19 harbors both canonical and noncanonical binding sites for the let-7 family of microRNAs, which plays important roles in development, cancer, and metabolism. Using H19 knockdown and overexpression, combined with in vivo crosslinking and genome-wide transcriptome analysis, we demonstrate that H19 modulates let-7 availability by acting as a molecular sponge. The physiological significance of this interaction is highlighted in culture where H19 depletion causes precocious muscle differentiation, a phenotype recapitulated by let-7 overexpression. Our results reveal an unexpected mode of action of H19 and identify this lncRNA as an important regulator of the major let-7 family of microRNAs.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/fbc3a9ee5608d5330d216a63504159e280a32727

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Citations in the corpus

Long Non-coding RNAs in the Cytoplasm (2016, background): “It is reported that H19 lncRNA acts as a molecular sponge for let-7 family of miRNAs in a HEK293 cell line [84].”
Transcriptional and Post-transcriptional Gene Regulation by Long Non-coding RNA (2017, methodology): “H19 contains let-7 binding sites and siRNAinduced depletion of H19 in mouse C2C12 muscle cells leads to reduced expression of let-7 target genes and increased expression of markers of muscle differentiation [53].”
Roles, Functions, and Mechanisms of Long Non-coding RNAs in Cancer (2016, background): “These lncRNAs modulate transcription by sequestering regulatory factors including transcription factors, catalytic proteins, subunits of larger chromatin modifying complexes, as well as miRNAs, thereby reducing their availability [22].”
Noncoding RNA:RNA Regulatory Networks in Cancer (2018, background): “A number of studies have also highlighted its binding preference to let-7 miRNAs, whilst H19 could also form a reciprocal negative feedback loop with the established let-7 target, as well as antagonist, LIN28 for breast cancer stem cell maintenance [60,61].”
The molecular mechanisms and therapeutic strategies of EMT in tumor progression and metastasis (2022, background): “H19 can mediate EMT by differentially binding to miR-200b, miR-200c, Let-7, SNAIL2, and Ezh2 [157].”