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Review
. 2023 Nov 15;115(19):1785-1808.
doi: 10.1002/bdr2.2178. Epub 2023 Apr 17.

The role of noncoding RNAs in pancreatic birth defects

Ziyue Zoey Yang  1   2   3   4 , Ronald J Parchem  1   2   3   4
Affiliations
Review

The role of noncoding RNAs in pancreatic birth defects

Ziyue Zoey Yang et al. Birth Defects Res. .

Abstract

Congenital defects in the pancreas can cause severe health issues such as pancreatic cancer and diabetes which require lifelong treatment. Regenerating healthy pancreatic cells to replace malfunctioning cells has been considered a promising cure for pancreatic diseases including birth defects. However, such therapies are currently unavailable in the clinic. The developmental gene regulatory network underlying pancreatic development must be reactivated for in vivo regeneration and recapitulated in vitro for cell replacement therapy. Thus, understanding the mechanisms driving pancreatic development will pave the way for regenerative therapies. Pancreatic progenitor cells are the precursors of all pancreatic cells which use epigenetic changes to control gene expression during differentiation to generate all of the distinct pancreatic cell types. Epigenetic changes involving DNA methylation and histone modifications can be controlled by noncoding RNAs (ncRNAs). Indeed, increasing evidence suggests that ncRNAs are indispensable for proper organogenesis. Here, we summarize recent insight into the role of ncRNAs in the epigenetic regulation of pancreatic development. We further discuss how disruptions in ncRNA biogenesis and expression lead to developmental defects and diseases. This review summarizes in vivo data from animal models and in vitro studies using stem cell differentiation as a model for pancreatic development.

Keywords: epigenetic regulation; lncRNA; miRNA; ncRNA; pancreatic birth defects; pancreatic development.

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Figures

Figure 1.
Figure 1.
Illustration of pancreatic development. Transcription factors and signaling pathways regulating pancreatic development are labeled in black. DNA methylation and histone modifications are labeled in orange.
Figure 2.
Figure 2.
Illustration of birth defects in the pancreas. (A) In a healthy pancreas, the ducts in the dorsal and ventral pancreas fuse to form a single duct, and the β-cells in the islet of Langerhans synthesize and secret insulin. (B) Agenesis of the pancreas with partially developed pancreas. (C) Failure in the fusion between dorsal and ventral ducts leads to pancreas divisum. (D) Formation of the annular pancreas. Instead of rotating with the gut tube and fusing with the dorsal pancreas, the ventral pancreas encircles the duodenum. (E) Insulin secretion is decreased due to β-cell loss in diabetes. Factors known to contribute to each birth defect are labeled in each panel.
Figure 3.
Figure 3.
The biogenesis and function of canonical miRNAs. The RNA Pol II or Pol III transcribes the miRNA gene to pri-miRNA, which then is processed by the microprocessor to form pre-miRNA. The pre-miRNA is exported to the cytoplasm by EXPORTIN5. In the cytoplasm, the pre-miRNA is cleaved by DICER to produce the miRNA duplex. The duplex is loaded onto AGO2. Only one strand will form the mature RISC with AGO2, and the other strand is ejected. The mature RISC will bind to target mRNA and silence gene expression by mRNA degradation or translational repression.
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