Mature Let-7 miRNAs fine tune expression of LIN28B in pluripotent human embryonic stem cells

Rahkonen, Nelly; Stubb, Aki; Malonzo, Maia; Edelman, Sanna; Emani, Maheswarareddy; Närvä, Elisa; Lähdesmäki, Harri; Ruohola‐Baker, Hannele; Lahesmaa, Riitta; Lund, Riikka

doi:10.1016/j.scr.2016.09.025

Cited by 18 publications

(16 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The mechanistic explanation for this is not known; however, recent studies have demonstrated that, in some CRC cell lines, overexpression of pluripotency factors (OCT3/4, SOX2, and KLF4) can lead to tumors with increased differentiation (Oshima et al 2014). This is in line with our finding, since LIN28B is also a pluripotency factor (Rahkonen et al 2016;Zhang et al 2016;Tsanov et al 2017), although this does not mean that pluripotency and differentiation are necessarily linked in this context.…”

Section: Imp1 Loss Enhances Lin28b-mediated Tumorigenesis In Vivosupporting

confidence: 88%

“…LIN28B is a critical pluripotency factor and is engaged in diverse cancer types, including CRC (Rahkonen et al 2016;Zhang et al 2016;Tsanov et al 2017). LIN28B acts to a major extent through the post-transcriptional down-regulation of the let-7 miR family.…”

Section: Discussionmentioning

confidence: 99%

“…As a master regulator of the let-7 family of microRNAs (miRs), LIN28B exerts its effects via suppression of let-7 processing and thus up-regulation of let-7 targets, including HMGA2 and IGF2BP1 (IMP1) (Boyerinas et al 2008;Piskounova et al 2011). In addition, LIN28B acts as a pluripotency factor and promotes tumorigenesis in multiple tissues (Viswanathan et al 2009;Tu et al 2015;Rahkonen et al 2016;Zhang et al 2016). We demonstrated previously that LIN28B overexpression promotes migration and invasion in vitro and that CRC cells overexpressing LIN28B exhibit smaller yet more metastatic tumors in subcutaneous xenograft mouse models.…”

mentioning

confidence: 99%

See 2 more Smart Citations

The LIN28B–IMP1 post-transcriptional regulon has opposing effects on oncogenic signaling in the intestine

et al. 2018

View full text Add to dashboard Cite

RNA-binding proteins (RBPs) are expressed broadly during both development and malignant transformation, yet their mechanistic roles in epithelial homeostasis or as drivers of tumor initiation and progression are incompletely understood. Here we describe a novel interplay between RBPs LIN28B and IMP1 in intestinal epithelial cells. Ribosome profiling and RNA sequencing identified as a principle node for gene expression regulation downstream from In vitro and in vivo data demonstrate that epithelial IMP1 loss increases expression of WNT target genes and enhances LIN28B-mediated intestinal tumorigenesis, which was reversed when we overexpressed IMP1 independently in vivo. Furthermore, IMP1 loss in wild-type or LIN28B-overexpressing mice enhances the regenerative response to irradiation. Together, our data provide new evidence for the opposing effects of the LIN28B-IMP1 axis on post-transcriptional regulation of canonical WNT signaling, with implications in intestinal homeostasis, regeneration and tumorigenesis.

show abstract

Section: Imp1 Loss Enhances Lin28b-mediated Tumorigenesis In Vivosupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

The LIN28B–IMP1 post-transcriptional regulon has opposing effects on oncogenic signaling in the intestine

et al. 2018

View full text Add to dashboard Cite

show abstract

“…As mentioned above, miRNAs function at the post-transcriptional level and have been demonstrated to be a promising approach for fine-tuning the excessive expression of their target genes in several biological processes (Rahkonen et al, 2016 ; Roy, 2016 ; Su et al, 2016 ). In addition, intranasal delivery of miRNA mimics and inhibitors, which can bypass the blood-brain barrier to deliver drugs into the brain, has been used recently to treat several neurological diseases (Ma et al, 2016 ; Lee et al, 2017 ; Tao et al, 2017 ).…”

Section: Dual Regulation By Mirnas In Epilepsymentioning

confidence: 99%

Conflicting Effects of Methylglyoxal and Potential Significance of miRNAs for Seizure Treatment

Tao

Zhou

Zhao

et al. 2018

Front. Mol. Neurosci.

View full text Add to dashboard Cite

According to an update from the World Health Organization, approximately 50 million people worldwide suffer from epilepsy, and nearly one-third of these individuals are resistant to the currently available antiepileptic drugs, which has resulted in an insistent pursuit of novel strategies for seizure treatment. Recently, methylglyoxal (MG) was demonstrated to serve as a partial agonist of the gamma-aminobutyric acid type A (GABAA) receptor and to play an inhibitory role in epileptic activities. However, MG is also a substrate in the generation of advanced glycation end products (AGEs) that function by activating the receptor of AGEs (RAGE). The AGE/RAGE axis is responsible for the transduction of inflammatory cascades and appears to be an adverse pathway in epilepsy. This study systematically reviewed the significance of GABAergic MG, glyoxalase I (GLO1; responsible for enzymatic catalysis of MG cleavage) and downstream RAGE signaling in epilepsy. This work also discussed the potential of miRNAs that target multiple mRNAs and introduced a preliminary scheme for screening and validating miRNA candidates with the goal of reconciling the conflicting effects of MG for the future development of seizure treatments.

show abstract

“…Можно предположить, что эти миРНК задействованы в процессе поддержания плюрипотентности у крысы. Кроме того, в данной сети участвуют миРНК, вовлеченные в процесс негативной регуляции плюрипотентного состояния клеток мыши и человека, такие как, например, miR145 и представители семейства let7 (Xu et al, 2009;Rahkonen et al, 2016). В сети представлены также миРНК семейства miR181, регулирующие Tcl1a и Wnt3a.…”

Section: результатыunclassified

The search for microRNAs potentially involved in the selfrenewal maintaining of laboratory rat pluripotent stem cells

Sherstyuk

Medvedev

et al. 2018

Vestn. VOGiS

View full text Add to dashboard Cite

Self-renewal of cultured pluripotent stem cells is a complex process, which includes multiple functional and regulatory levels. Transcription factors, their target genes, chromatin modifiers, signaling pathways, and regulatory noncoding RNAs are involved in the maintaining of self-renewal. Studies of molecular and genetic bases of maintaining self-renewal and pluripotency in cultured mammalian cells are important to understand processes in preimplantation embryogenesis and to develop efficient techniques to obtain pluripotent stem cell lines for experimental biology and medicine. MicroRNAs (miRNAs) play an important role in pluripotency maintaining and reprogramming. However, involvement of this class of noncoding RNAs and functions of individual molecules are poorly studied. The goal of this study was the search for the miRNAs potentially involved in the pluripotency maintaining and reprogramming of Rattus norvegicus cells. We analyzed the expression of miRNAs in rat embryonic stem cells, induced pluripotent stem cells and embryonic fibroblasts using bioinformatic methods and data obtained with next generation sequencing. The analysis of differential expression between groups of rat pluripotent cells and fibroblasts, and the analysis of experimentally confirmed target genes of differentially expressed known rat miRNAs revealed novel potential players of pluripotency maintaining and reprogramming processes. In addition, novel members of these processes were revealed among novel rat miRNAs. The use of bioinformatic and systems biology approaches is the first step, which is necessary for choosing candidates for the subsequent experimental studies. The results obtained substantially improve our understanding of the self-renewal regulation system of the laboratory rat, a popular biomedical object, and our knowledge about the system in mammals.

show abstract

Mature Let-7 miRNAs fine tune expression of LIN28B in pluripotent human embryonic stem cells

Cited by 18 publications

References 43 publications

The LIN28B–IMP1 post-transcriptional regulon has opposing effects on oncogenic signaling in the intestine

The LIN28B–IMP1 post-transcriptional regulon has opposing effects on oncogenic signaling in the intestine

Conflicting Effects of Methylglyoxal and Potential Significance of miRNAs for Seizure Treatment

The search for microRNAs potentially involved in the selfrenewal maintaining of laboratory rat pluripotent stem cells

Contact Info

Product

Resources

About