The DOI matches its Crossref record; 5 of the 5 references it cites were found in a registry or an index.
The LIN28/let-7 Pathway in Cancer
Open accessAbstract
Among all tumor suppressor microRNAs, reduced let-7 expression occurs most frequently in cancer and typically correlates with poor prognosis. Activation of either LIN28A or LIN28B, two highly related RNA binding proteins (RBPs) and proto-oncogenes, is responsible for the global post-transcriptional downregulation of the let-7 microRNA family observed in many cancers. Specifically, LIN28A binds the terminal loop of precursor let-7 and recruits the Terminal Uridylyl Transferase (TUTase) ZCCHC11 that polyuridylates pre-let-7, thereby blocking microRNA biogenesis and tumor suppressor function. For LIN28B, the precise mechanism responsible for let-7 inhibition remains controversial. Functionally, the decrease in let-7 microRNAs leads to overexpression of their oncogenic targets such as MYC, RAS, HMGA2, BLIMP1, among others. Furthermore, mouse models demonstrate that ectopic LIN28 expression is sufficient to drive and/or accelerate tumorigenesis via a let-7 dependent mechanism. In this review, the LIN28/let-7 pathway is discussed, emphasizing its role in tumorigenesis, cancer stem cell biology, metabolomics, metastasis, and resistance to ionizing radiation and several chemotherapies. Also, emerging evidence will be presented suggesting that molecular targeting of this pathway may provide therapeutic benefit in cancer.
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Cites
Induced Pluripotent Stem Cell Lines Derived from Human Somatic Cells
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Lin28 recruits the TUTase Zcchc11 to inhibit let-7 maturation in mouse embryonic stem cells
Hagan, J. P., Piskounova, E., & Gregory, R. I. (2009) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.1676 · Cited by 491
Self-citationA role for the Perlman syndrome exonuclease Dis3l2 in the Lin28–let-7 pathway
Chang, H.-M., Triboulet, R., Thornton, J. E., & Gregory, R. I. (2013) · Nature · doi:10.1038/nature12119 · Cited by 341
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Hovestadt, V., Ayrault, O., Swartling, F. J., Robinson, G. W., Pfister, S. M., & Northcott, P. A. (2020) · Nature Reviews Cancer · doi:10.1038/s41568-019-0223-8 · Cited by 271
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RNA‐PROTACs: Degraders of RNA‐Binding Proteins
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Metadata
- Authors
- Balzeau, J., Menezes, M. R., Cao, S., & Hagan, J. P.
- Venue
- Frontiers in Genetics
- Publisher
- Frontiers Media SA
- Published
- 2017-03-28
- Volume
- 8
- Pages
- 31-31
- ISSN
- 1664-8021 (ISSN-L)
- OpenAlex
- W2597435890
- Cited by
- 447
- References
- 5
- FWCI
- 14.25
- Type
- journal article
- Language
- en
- Open access
- gold
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