LIN28B and Let-7 in Diffuse Midline Glioma: A Review

Knowles, Tuomas P. J.; Huang, Tina; Qi, Jin; An, Shejuan; Burket, Noah; Cooper, Scott; Nazarian, Javad; Saratsis, Amanda

doi:10.3390/cancers15123241

Cited by 6 publications

(2 citation statements)

References 155 publications

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“…Reduced levels of Mirlet7 family members have been related to less-differentiated cellular stages and to different cancers [ 60 , 61 ]. Interestingly, LIN28B and its paralog, LIN28A, interact with the primary and/or preliminary transcripts of various members of the Mirlet7 family during development and oncogenesis and suppress the biogenesis of the mature miRNAs [ 62 , 63 , 64 , 65 , 66 ]. LIN28A together with Musashi1 (MSI1) sequester pri-Mirlet7 in the cell nucleus [ 66 ].…”

Section: Nuclear Mirnas and Their Implications In Cancermentioning

confidence: 99%

Implications in Cancer of Nuclear Micro RNAs, Long Non-Coding RNAs, and Circular RNAs Bound by PRC2 and FUS

Swaminathan,

Rogel-Ayala,

Armich

et al. 2024

Cancers

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The eukaryotic genome is mainly transcribed into non-coding RNAs (ncRNAs), including different RNA biotypes, such as micro RNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), among others. Although miRNAs are assumed to act primarily in the cytosol, mature miRNAs have been reported and functionally characterized in the nuclei of different cells. Further, lncRNAs are important regulators of different biological processes in the cell nucleus as part of different ribonucleoprotein complexes. CircRNAs constitute a relatively less-characterized RNA biotype that has a circular structure as result of a back-splicing process. However, circRNAs have recently attracted attention in different scientific fields due to their involvement in various biological processes and pathologies. In this review, we will summarize recent studies that link to cancer miRNAs that have been functionally characterized in the cell nucleus, as well as lncRNAs and circRNAs that are bound by core components of the polycomb repressive complex 2 (PRC2) or the protein fused in sarcoma (FUS), highlighting mechanistic aspects and their diagnostic and therapeutic potential.

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Section: Nuclear Mirnas and Their Implications In Cancermentioning

confidence: 99%

Implications in Cancer of Nuclear Micro RNAs, Long Non-Coding RNAs, and Circular RNAs Bound by PRC2 and FUS

Swaminathan,

Rogel-Ayala,

Armich

et al. 2024

Cancers

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“…Regulation via the LIN28/let-7 axis is such that LIN28 and let-7 have opposite effects on developmental progression [41]. In order to promote differentiation programming, each of the let-7 family members decrease expression of genes that promote stemness, proliferation, and migration, whereas LIN28A/B derepresses these genes in a let-7-dependent way to maintain a pluripotent phenotype [42]. This provides a let-7dependent mechanism of oncogene upregulation; as such, the LIN28/let-7 axis has been shown to regulate cancer development in various ways (Figure 3).…”

Section: Mechanistic Studies On the Regulation Of Cancer Progression ...mentioning

confidence: 99%

Regulating Protein–RNA Interactions: Advances in Targeting the LIN28/Let-7 Pathway

Oyejobi,

Yan,

Sliz

et al. 2024

IJMS

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Originally discovered in C. elegans, LIN28 is an evolutionarily conserved zinc finger RNA-binding protein (RBP) that post-transcriptionally regulates genes involved in developmental timing, stem cell programming, and oncogenesis. LIN28 acts via two distinct mechanisms. It blocks the biogenesis of the lethal-7 (let-7) microRNA (miRNA) family, and also directly binds messenger RNA (mRNA) targets, such as IGF-2 mRNA, and alters downstream splicing and translation events. This review focuses on the molecular mechanism of LIN28 repression of let-7 and current strategies to overcome this blockade for the purpose of cancer therapy. We highlight the value of the LIN28/let-7 pathway as a drug target, as multiple oncogenic proteins that the pathway regulates are considered undruggable due to their inaccessible cellular location and lack of cavities for small molecule binding.

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The RAS oncogene in brain tumors and the involvement of let-7 microRNA

Messina

2024

Mol Biol Rep

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RAS oncogenes are master regulator genes in many cancers. In general, RAS-driven cancers have an oncogenic RAS mutation that promotes disease progression (colon, lung, pancreas). In contrast, brain tumors are not necessarily RAS-driven cancers because RAS mutations are rarely observed. In particular, glioblastomas (the most lethal brain tumor) do not appear to have dominant genetic mutations that are suitable for targeted therapy. Standard treatment for most brain tumors continues to focus on maximal surgical resection, radiotherapy and chemotherapy. Yet the convergence of genomic aberrations such as EGFR, PDGFR and NF1 (some of which are clinically effective) with activation of the RAS/MAPK cascade is still considered a key point in gliomagenesis, and KRAS is undoubtedly a driving gene in gliomagenesis in mice. In cancer, microRNAs (miRNA) are small, non-coding RNAs that regulate carcinogenesis. However, the functional consequences of aberrant miRNA expression in cancer are still poorly understood. let-7 encodes an intergenic miRNA that is classified as a tumour suppressor, at least in lung cancer. Let-7 suppresses a plethora of oncogenes such as RAS, HMGA, c-Myc, cyclin-D and thus suppresses cancer development, differentiation and progression. let-7 family members are direct regulators of certain RAS family genes by binding to the sequences in their 3′untranslated region (3′UTR). let-7 miRNA is involved in the malignant behaviour in vitro—proliferation, migration and invasion—of gliomas and stem-like glioma cells as well as in vivo models of glioblastoma multiforme (GBM) via KRAS inhibition. It also increases resistance to certain chemotherapeutic agents and radiotherapy in GBM. Although let-7 therapy is not yet established, this review updates the current state of knowledge on the contribution of miRNA let-7 in interaction with KRAS to the oncogenesis of brain tumours.

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LIN28B and Let-7 in Diffuse Midline Glioma: A Review

Cited by 6 publications

References 155 publications

Implications in Cancer of Nuclear Micro RNAs, Long Non-Coding RNAs, and Circular RNAs Bound by PRC2 and FUS

Implications in Cancer of Nuclear Micro RNAs, Long Non-Coding RNAs, and Circular RNAs Bound by PRC2 and FUS

Regulating Protein–RNA Interactions: Advances in Targeting the LIN28/Let-7 Pathway

The RAS oncogene in brain tumors and the involvement of let-7 microRNA

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