LIN28: roles and regulation in development and beyond

Tsialikas, Jennifer; Romer-Seibert, Jennifer S.

doi:10.1242/dev.117580

Cited by 159 publications

(153 citation statements)

References 80 publications

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“…Just as LIN-28 governs transitions between undifferentiated and differentiated states (Shyh-Chang et al, 2013;Rougvie and Moss, 2013;Thornton and Gregory, 2012;Tsialikas and Romer-Seibert, 2015), upregulation of Mkrns in vertebrates is often linked with differentiation. For example, mouse and human Mkrn3 are expressed in differentiated cells derived from ESCs and are not expressed in proliferating ESCs (Jong et al, 1999a;Mai et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

“…For example, LIN-28 is involved in the transition between stemness and differentiation in normal development, wound healing, induced pluripotent stem cells and cancer (ShyhChang et al, 2013;Thornton and Gregory, 2012;Tsialikas and Romer-Seibert, 2015). Another transition regulated by LIN-28 is the juvenile-to-adult (J/A) transition in mammals, flies and nematodes Tsialikas and RomerSeibert, 2015).…”

Section: Introductionmentioning

confidence: 99%

“…It is increasingly clear from studies in several systems that lin-28 usually works with two other genes, let-7 and lin-41/Trim71, in a conserved 'axis' of negative interactions Tsialikas and Romer-Seibert, 2015). Besides being involved in the J/A transition, this axis controls many stemness-differentiation transitions.…”

Section: Introductionmentioning

confidence: 99%

“…Besides being involved in the J/A transition, this axis controls many stemness-differentiation transitions. LIN-28 is highly expressed in undifferentiated embryonic stem cells (ESCs) and declines during subsequent development Tsialikas and Romer-Seibert, 2015). LIN-28 inhibits the biogenesis of the mature form of the let-7 microRNA (miRNA) (Newman et al, 2008;Piskounova et al, 2008;Van Wynsberghe et al, 2011;Viswanathan et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

“…LIN-28 inhibits the biogenesis of the mature form of the let-7 microRNA (miRNA) (Newman et al, 2008;Piskounova et al, 2008;Van Wynsberghe et al, 2011;Viswanathan et al, 2008). When LIN-28 is downregulated, mature let-7 miRNA is produced, directing cells toward differentiated/adult fates (Copley et al, 2013;Hayes and Ruvkun, 2006;Rybak et al, 2008;Thornton and Gregory, 2012;Tsialikas and Romer-Seibert, 2015;Yu et al, 2007) by inhibiting the translation of primarily lin-41 and other target mRNAs (Ecsedi and Grosshans, 2013;Long et al, 2007;Slack et al, 2000;Vella et al, 2004a,b). homologs are proposed to silence the translation of target mRNAs (Ecsedi and Grosshans, 2013;Ecsedi et al, 2015;Loedige et al, 2013;Sonoda and Wharton, 2001;Vella et al, 2004a,b) that otherwise promote an undifferentiated/juvenile state (Chang et al, 2012;Ecsedi and Grosshans, 2013;Rybak et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

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LEP-2/Makorin regulates LIN-28 stability to promote the juvenile-to-adult transition in Caenorhabditis elegans

2016

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The heterochronic genes lin-28, let-7 and lin-41 regulate fundamental developmental transitions in animals, such as stemness versus differentiation and juvenile versus adult states. We identify a new heterochronic gene, lep-2, in Caenorhabditis elegans. Mutations in lep-2 cause a delay in the juvenile-to-adult transition, with adult males retaining pointed, juvenile tail tips, and displaying defective sexual behaviors. In both sexes, lep-2 mutants fail to cease molting or produce an adult cuticle. We find that LEP-2 post-translationally regulates LIN-28 by promoting LIN-28 protein degradation. lep-2 encodes the sole C. elegans ortholog of the Makorin (Mkrn) family of proteins. Like lin-28 and other heterochronic pathway members, vertebrate Mkrns are involved in developmental switches, including the timing of pubertal onset in humans. Based on shared roles, conservation and the interaction between lep-2 and lin-28 shown here, we propose that Mkrns, together with other heterochronic genes, constitute an evolutionarily ancient conserved module regulating switches in development.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

LEP-2/Makorin regulates LIN-28 stability to promote the juvenile-to-adult transition in Caenorhabditis elegans

2016

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The role of Lin28A and Lin28B in cancer beyond Let‐7

Cotino‐Nájera,

García‐Villa,

Cruz‐Rosales

et al. 2024

FEBS Letters

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Lin28A and Lin28B are paralogous RNA‐binding proteins that play fundamental roles in development and cancer by regulating the microRNA family of tumor suppressor Let‐7. Although Lin28A and Lin28B share some functional similarities with Let‐7 inhibitors, they also have distinct expression patterns and biological functions. Increasing evidence indicates that Lin28A and Lin28B differentially impact cancer stem cell properties, epithelial‐mesenchymal transition, metabolic reprogramming, and other hallmarks of cancer. Therefore, it is important to understand the overexpression of Lin28A and Lin28B paralogs in specific cancer contexts. In this review, we summarize the main similarities and differences between Lin28A and Lin28B, their implications in different cellular processes, and their role in different types of cancer. In addition, we provide evidence of other specific targets of each lin28 paralog, as well as the lncRNAs and miRNAs that promote or inhibit its expression, and how this impacts cancer development and progression.

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Lin28a enhances in vitro osteoblastic differentiation of human periosteum‐derived cells

Park

Kang

et al. 2017

Cell Biochemistry & Function

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Despite a capacity for proliferation and an ability to differentiate into multiple cell types, in long-term culture and with ageing, stem cells show a reduction in growth, display a decrease in differentiation potential, and enter senescence without evidence of transformation. The Lin28a gene encodes an RNA-binding protein that plays a role in regulating stem cell activity, including self-renewal and differentiation propensity. However, the effect of the Lin28a gene on cultured human osteoprecursor cells is poorly understood. In the present study, alkaline phosphatase activity, alizarin red-positive mineralization, and calcium content, positive indicators of osteogenic differentiation, were significantly higher in cultured human periosteum-derived cells (hPDCs) with Lin28a overexpression compared with cells without Lin28a overexpression. Lin28a overexpression by hPDCs also increased mitochondrial activity, which is essential for cellular proliferation, as suggested by a reduced presence of reactive oxygen species and significantly enhanced lactate levels and ATP production. Our results suggest that, in hPDCs, the Lin28a gene enhances osteoblastic differentiation and increases mitochondrial activity. Although Lin28a is known as a marker of undifferentiated human embryogenic stem cell, there is limited evidence regarding the influence of Lin28a on osteoblastic differentiation of cultured osteoprecursor cells. This study was to examine the impact of Lin28a on osteogenic phenotypes of human periosteum-derived cells. Their phenotypes can be similar to those of mesenchymal stem cells. Our results suggest that the Lin28a gene enhances the osteoblastic differentiation of human periosteum-derived cells. In addition, the Lin28a gene increases mitochondrial activity in human periosteum-derived cells.

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LIN28: roles and regulation in development and beyond

Cited by 159 publications

References 80 publications

LEP-2/Makorin regulates LIN-28 stability to promote the juvenile-to-adult transition in Caenorhabditis elegans

LEP-2/Makorin regulates LIN-28 stability to promote the juvenile-to-adult transition in Caenorhabditis elegans

The role of Lin28A and Lin28B in cancer beyond Let‐7

Lin28a enhances in vitro osteoblastic differentiation of human periosteum‐derived cells

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