Regulation of mouse stomach development and Barx1 expression by specific microRNAs

Kim, Byeong–Moo; Woo, Janghee; Kanellopoulou, Chryssa; Shivdasani, Ramesh A.

doi:10.1242/dev.056317

Cited by 22 publications

(21 citation statements)

References 31 publications

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“…miRNAs negatively regulate gene expression, the readout of miRNAs depends on the function of the target genes. MiR‐203 has been demonstrated to have multiple functions in different contexts, such as epidermal differentiation, gastric epithelium formation and cancer cell senescence . A number of targets of miR‐182 are important in immune responses, development of sensory organs and cell cycle in cancer cells .…”

Section: Discussionmentioning

confidence: 99%

MiR‐182 and miR‐203 induce mesenchymal to epithelial transition and self‐sufficiency of growth signals via repressing SNAI2 in prostate cells

Hellem

et al. 2013

Intl Journal of Cancer

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MicroRNAs play critical roles in tumorigenesis and metastasis. Here, we report the dual functions of miR-182 and miR-203 in our previously described prostate cell model. MiR-182 and miR-203 were completely repressed during epithelial to mesenchymal transition (EMT) from prostate epithelial EP156T cells to the progeny mesenchymal nontransformed EPT1 cells. Re-expression of miR-182 or miR-203 in EPT1 cells and prostate cancer PC3 cells induced mesenchymal to epithelial transition (MET) features. Simultaneously, miR-182 and miR-203 provided EPT1 cells with the ability to self-sufficiency of growth signals, a well-recognized oncogenic feature. Gene expression profiling showed high overlap of the genes affected by miR-182 and miR-203. SNAI2 was identified as a common target of miR-182 and miR-203. Knock-down of SNAI2 in EPT1 cells phenocopied reexpression of either miR-182 or miR-203 regarding both MET and self-sufficiency of growth signals. Strikingly, considerable overlaps of changed genes were found between the re-expression of miR-182/203 and knock-down of SNAI2. Finally, P-cadherin was identified as a direct target of SNAI2. We conclude that miR-182 and miR-203 induce MET features and growth factor independent growth via repressing SNAI2 in prostate cells. Our findings shed new light on the roles of miR-182/203 in cancer related processes.The breakdown of epithelial cell homeostasis with the loss of epithelial characteristics and the acquisition of a migratory phenotype, referred to as epithelial to mesenchymal transition (EMT) is a crucial event in tumor progression and endows cancer cells with invasive and metastatic competence.1 Prostate cancer is one of the most common male cancers in Western countries. In an attempt to transform benign prostate cells to malignant ones, we have observed typical EMT features in primary prostate basal EP156T cells.2 However, both EP156T and the progeny EPT1 cells lacked malignant features such as anchorage independent growth, resistance to apoptosis and independence of external growth factors. 2,3 This unique EMT cell model provides a good opportunity to understand the mechanisms of EMT and malignant transformation in vitro.MicroRNAs (miRNAs/miRs) are a large class of endogenous tiny regulatory RNAs that extensively regulate gene expression. MiRNAs function post-transcriptionally through imperfect base pairing with specific sequences in the 3 0 untranslated regions (UTRs) of target mRNAs leading to transcript degradation or translational inhibition. 4 The role of miRNAs depends not only on their specific mRNA targets but also upon their context, such as cell type, tissue or stage of development. MiRNAs are widely recognized as important in tumor progression, it has been considered that alterations in the expression of miRNAs might contribute to the pathogenesis of most human malignancies.5 However, most of these studies utilized cancer cells, examination of the function of miRNAs in premalignant cells is thus far limited.Exploiting our unique premalignant EPT1 cell model that ...

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Section: Discussionmentioning

confidence: 99%

MiR‐182 and miR‐203 induce mesenchymal to epithelial transition and self‐sufficiency of growth signals via repressing SNAI2 in prostate cells

Hellem

et al. 2013

Intl Journal of Cancer

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“…Early formation of the gastro-intestinal boundary is orchestrated by a mesenchymal-epithelial network that was elucidated in a key series of papers on the transcription factor Barx1 [50,51]. This factor is specifically expressed in the presumptive stomach mesenchyme, and it promotes expression of secreted WNT signaling antagonists (sFRPs) in this region.…”

Section: Specification Of Gastric Lineagementioning

confidence: 99%

Mechanisms of embryonic stomach development

McCracken

Wells

2017

Seminars in Cell & Developmental Biology

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The stomach is a digestive organ that has important roles in human physiology and pathophysiology. The developmental origin of the stomach is the embryonic foregut, which also gives rise a number of other structures. There are several signaling pathways and transcription factors that are known to regulate stomach development at different stages, including foregut patterning, stomach specification, and gastric regionalization. These developmental events have important implications in later homeostasis and disease in the adult stomach. Here we will review the literature that has shaped our current understanding of the molecular mechanisms that coordinate gastric organogenesis. Further we will discuss how developmental paradigms have guided recent efforts to differentiate stomach tissue from pluripotent stem cells.

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“…It is worth noting in this regard that Hoxa5 -/- mice, which also have a partially intestinalized hindstomach, show reduced Barx1 expression [28]. Furthermore, selected microRNAs that appear late in stomach development, including miR-7a and miR-203, serve to restrict Barx1 expression temporally and perhaps also spatially [29]. Additional investigation of Barx1 gene regulation will shed useful light.…”

Section: The Stomach-duodenum Boundarymentioning

confidence: 99%

Boundaries, junctions and transitions in the gastrointestinal tract

Roman

Shivdasani

2011

Experimental Cell Research

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Contiguous regions along the mammalian gastrointestinal tract, from the esophagus to the rectum, serve distinct digestive functions. Some organs, such as the esophagus and glandular stomach or the small bowel and colon, are separated by sharp boundaries. The duodenal, jejunal and ileal segments of the small intestine, by contrast, have imprecise borders. Because human esophageal and gastric cancers frequently arise in a background of tissue metaplasia and some intestinal disorders are confined to discrete regions, it is useful to appreciate the molecular and cellular basis of boundary formation and preservation. Here we review the anatomy and determinants of boundaries and transitions in the alimentary canal with respect to tissue morphology, gene expression, and, especially, transcriptional control of epithelial identity. We discuss the evidence for established and candidate molecular mechanisms of boundary formation, including the solitary and combinatorial actions of tissue-restricted transcription factors. Although the understanding remains sparse, genetic studies in mice do provide insights into dominant mechanisms and point the way for future investigation.

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Regulation of mouse stomach development and Barx1 expression by specific microRNAs

Cited by 22 publications

References 31 publications

MiR‐182 and miR‐203 induce mesenchymal to epithelial transition and self‐sufficiency of growth signals via repressing SNAI2 in prostate cells

MiR‐182 and miR‐203 induce mesenchymal to epithelial transition and self‐sufficiency of growth signals via repressing SNAI2 in prostate cells

Mechanisms of embryonic stomach development

Boundaries, junctions and transitions in the gastrointestinal tract

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