Comprehensive analysis of microRNA signature of mouse pancreatic acini: overexpression of miR-21-3p in acute pancreatitis

Abstract

In the current study, we have characterized the global miRNA expression profile in mouse pancreatic acinar cells and during acute pancreatitis using next-generation RNA sequencing. We identified 324 known and six novel miRNAs that are expressed in mouse pancreatic acinar cells. In the basal state, miR-148a-3p, miR-375-3p, miR-217-5p, and miR-200a-3p were among the most abundantly expressed, whereas miR-24-5p and miR-421-3p were the least abundant. Treatment of acinar cells with caerulein (100 nM) and taurolithocholic acid 3-sulfate [TLC-S (250 μM)] induced numerous changes in miRNA expression profile. In particular, we found significant overexpression of miR-21-3p in acini treated with caerulein and TLC-S. We further looked at the expression of miR-21-3p in caerulein, l-arginine, and caerulein + LPS-induced acute pancreatitis mouse models and found 12-, 21-, and 50-fold increased expression in the pancreas, respectively. In summary, this is the first comprehensive analysis of global miRNA expression profile of mouse pancreatic acinar cells in normal and disease conditions. Our analysis shows that miR-21-3p expression level correlates with the severity of the disease.

MicroRNA‐351‐5p aggravates intestinal ischaemia/reperfusion injury through the targeting of MAPK13 and Sirtuin‐6

“…Among them, 18 up‐regulated miRNAs (miR‐23a‐5p, miR‐300‐5p, miR‐21‐3p, miR‐344b‐1‐3p, miR‐351‐5p, miR‐874‐3p, miR‐144‐3p, miR‐3572, miR‐27a‐5p, miR‐183‐3p, miR‐294, miR‐451‐5p, miR‐483‐3p, miR‐883‐5p, miR‐125b‐2‐3p, miR‐3573‐3p, miR‐485‐3p and miR‐490‐5p) and 12 down‐regulated miRNAs (miR‐181c‐5p, miR‐187‐3p, miR‐532‐5p, miR‐194‐5p, miR‐203a‐3p, miR‐17‐1‐3p, miR‐192‐5p, miR‐28‐3p, miR‐140‐5p, miR‐142‐3p, miR‐29c‐3p and miR‐362‐3p) with clear statistical significance ( P <0.05 different from control values) were identified. Furthermore, nine miRNAs ‐ miR‐144‐3p, miR‐3572, miR‐27a‐5p, miR‐142‐3p, miR‐23a‐5p, miR‐21‐3p, miR‐294, miR‐351‐5p and miR‐362‐3p ‐ associated with oxidative stress, inflammation and apoptosis (Romay et al ., ; Wang et al ., ; da Silva et al ., ; Dixit et al ., ; Brea et al ., ; Chen et al ., ; Li et al ., ) were selected for validation by real‐time PCR assay in IEC‐6 cells and rats. These results, shown in Figure B, were consistent with the results of the microarray assays.…”

“…All data are expressed as the mean ± SD. * P < 0.05, significantly different from control group; # P < 0.05, significantly different from the 60 min reoxygenation or 90 min reperfusion group.miRNA-351-5p aggravates II/R injury 351-5p and miR-362-3p -associated with oxidative stress, inflammation and apoptosis(Romay et al, 2015;Wang et al, 2015;da Silva et al, 2016;Dixit et al, 2016;Brea et al, 2017;Chen et al, 2017;Li et al, 2018) were selected for validation by real-time PCR assay in IEC-6 cells and rats. These results, shown inFigure 3B, were consistent with the results of the microarray assays.…”

CircRNA Expression Profiles and the Potential Role of CircZFP644 in Mice With Severe Acute Pancreatitis via Sponging miR-21-3p

“…The miR-21 family is known to be overexpressed in human specimens and experimental models in SAP, and plays an important role in the development and progression of the disease. It has been reported that miR-21-3p is overexpressed in the pathological state of acinar cells that have been overdosed with caerulein or sodium taurocholate rather than caerulein in physiological doses (Dixit et al, 2016). Additionally, the overexpression of miR-21-3p in acinar cells inhibited apoptosis (Wang et al, 2018), which nullifies the protective effects of apoptosis for preventing leakage of necrotic substances and limiting inflammation (Najenson et al, 2018), and also promotes necroptosis of pancreatic acinar cells (Ma et al, 2015), thereby aggravating the injury of pancreatic tissues.…”

Targeting MicroRNA Function in Acute Pancreatitis

“…Moreover, Kong et al quantified the relative concentration of miR-216a in pancreas tissues sampled from healthy rats, and found it was 128-fold higher than that in kidney, which had the next highest concentration, indicating that miR-216a may contribute to distinguishing pancreatic diseases from other tissue diseases (Kong et al, 2010 ). Dixit et al identified that miR-148a-3p, miR-375-3p, miR-217-5p, and miR-200a-3p are the most abundant miRNAs at basal state, whereas miR-421-3p, miR-24-5p, and miR-29a-5p are the least abundantly expressed in mouse pancreatic acinar cells (Dixit et al, 2016 ). In addition, Let-7b and miR-495 and their target genes control a transcriptional network that drives pancreatic acinar cell differentiation, which are critical to ensuring acinar homeostasis (Prevot et al, 2013 ).…”

“…At present, the pancreatic biomarkers amylase and lipase are commonly used in the early prediction of AP, but they are often limited in clinical practice due to their own limitations (Treacy et al, 2001 ; Huang et al, 2016 ). Accumulating evidence has shown that abnormal expression of miRNA related to AP pathogenesis can serve as a candidate biomarker of this disease diagnosis and prognosis (Kong et al, 2010 ; An et al, 2014 ; Dixit et al, 2016 ; Zhang et al, 2017 ). The aberrant miRNA expression patterns in animal models and patients with AP are listed in Table 1 .…”