miR-375 Promotes Pancreatic Differentiation In Vitro by Affecting Different Target Genes at Different Stages

Abstract

Human embryonic stem cells (hESCs) possess the ability to differentiate into insulin-producing cells (IPCs), which can be used to treat type I diabetes. miR-375 is an essential transcriptional regulator in the development and maturation of the pancreas. In this study, we optimized a protocol to differentiate hESCs into IPCs and successfully obtained IPCs. Then, we performed overexpression and inhibition experiments of miR-375 on cells at different stages of differentiation and performed RNA-seq. The results showed that the expression of miR-375 fluctuated during hESC differentiation and was affected by miR-375 mimics and inhibitors. miR-375 influences global gene expression and the target genes of miR-375. The overexpression of miR-375 can cause changes in multiple signaling pathways during pancreatic development. miR-375 is a major participant in the differentiation of pancreatic β-cells through different target genes at different stages. This study provides new ideas for further investigation of how microRNAs affect cell fate and gene transcription.

CircRPPH1 promotes the stemness of gastric cancer cells by targeting miR‐375/SLC7A11 axis

“…24 In consistent, the recent study indicated that miR-375 promotes pancreatic differentiation in vitro by affecting different target genes at different stages. 25 Since CSCs always share the same survival mechanisms with normal stem cells, miR-375 was regarded to be involved in CSC progression, which was further confirmed by several studies. 5,6,26 Besides, miR-375 was indicated to exert anti-tumorigenic effects via regulating tumor microenvironment (TME).…”

“…MiR‐375 has been shown to control normal stem cell differentiation, such as miR‐375 controls porcine pancreatic stem cell fate by targeting 3‐phosphoinositide‐dependent protein kinase‐1 (Pdk1) 23 ; Overexpression of miR‐375 promotes the differentiation of human‐induced pluripotent stem cells into hepatocyte‐like cells 24 . In consistent, the recent study indicated that miR‐375 promotes pancreatic differentiation in vitro by affecting different target genes at different stages 25 . Since CSCs always share the same survival mechanisms with normal stem cells, miR‐375 was regarded to be involved in CSC progression, which was further confirmed by several studies 5,6,26 .…”

MicroRNA-375: potential cancer suppressor and therapeutic drug

“…For example, the overexpression of miR-375 in MIN6 cells could inhibit glucose-induced insulin secretion. Thus, miR-375 could be a potential biomarker for the treatment of diabetes [ 100 ]. In cancer cells, glucose is preferentially metabolized through aerobic glycolysis, increasing the production of glycolysis and lactic acid.…”

Differentially expressed microRNAs during the differentiation of muscle-derived stem cells into insulin-producing cells, a promoting role of microRNA-708-5p/STK4 axis

“…MicroRNAs (miRNAs) are endogenous small-non-coding RNAs, which act as crucial regulatory roles in gene expression by complementary binding to the 3'-untranslated regions (3'-UTR) of target mRNAs [8]. Numerous evidences have supported that miRNAs are involved in the differentiation of various stem cells into IPCs by regulating target genes [9][10][11]. For instance, miRNA-375 promoted the differentiation of human embryonic stem cells into IPCs by affecting its target genes and pancreatic development-related genes, including PDPK1, INSM1, HNF1B, GATA6, NOTCH2, PAX6, and CADM1 [9].…”

“…Numerous evidences have supported that miRNAs are involved in the differentiation of various stem cells into IPCs by regulating target genes [9][10][11]. For instance, miRNA-375 promoted the differentiation of human embryonic stem cells into IPCs by affecting its target genes and pancreatic development-related genes, including PDPK1, INSM1, HNF1B, GATA6, NOTCH2, PAX6, and CADM1 [9]. miRNA-690 facilitated the differentiation of induced pluripotent stem cells into IPCs by targeting Sox9 [11].…”