Upregulated exosomic miR-23b-3p plays regulatory roles in the progression of pancreatic cancer

Abstract

Pancreatic cancer (PC) is one of the most lethal malignances. Identification of biomarkers for early diagnosis of PC is a key imperative. MicroRNAs (miRNAs) have been shown to be valuable biomarkers in the context of several cancers. Exosomes refer to vesicles released by the tumor cells at the early stage of disease. Thus, detection of miRNA in exosomes can be used as a potential biomarker for PC. In this study, we profiled serum levels of miRNAs in patients with chronic pancreatitis (CP) and PC; the role of miR-23b-3p in PC progression was assessed in vitro. Additionally, we assessed, the expression of miR-23b-3p in exosomes isolated from serum samples and assessed the correlation between the expression of miR-23b-3p and carbohydrate antigen 19-9 (CA19-9). Three serum samples each were randomly selected from healthy controls (n=20), and patients with CP (n=18) and PC (n=16) for miRNA microarray profiling. The dysregulated miRNAs were confirmed using qRT-PCR. Four dysregulated miRNAs common to patients with CP and PC were identified on miRNA microarray analysis and confirmed by qRT-PCR. miR-23b-3p level was consistently higher in serum samples from PC patients as compared to those from healthy controls and CP patients (p<0.05). Overexpression of miR-23b-3p promoted proliferation, migration, and invasion capability of PC cells in vitro (p<0.05). Furthermore, miR-23b-3p was upregulated in exosomes of PC serum samples and the supernatant of pancreatic cancer cells (PANC-1), and the expression levels of miR-23b-3p were associated with those of serum CA19-9 levels. This study provides insights into the potential role of miR-23b-3p as a novel biomarker and target for treatment of PC.

Effect of exosomal miRNA on cancer biology and clinical applications

“… Proliferation [ 108 ] miR-221-3p Inhibitor miR-23b-3p PANC-1 cells PANC-1 cells CA-19-9 miR-23b-3p expression in sera or that in the exosomes isolated from sera showed a close relationship with CA-19-9 expression. Proliferation and metastasis [ 103 , 109 ] miR-141, miR-375 PCa cells Serum / miR-141 and miR-375 were associated with recurrent (metastatic) PCa following radical prostatectomy metastasis [ 110 ] miR-1290, miR-375 PCa cells Plasma / Various RNA species and changes in exosomal RNA contents are robust candidates as clinical biomarkers for advanced PCa Survival prognosis [ 111 ] miR-19b PCa cells Urine / Active secretion of miR-19b containing vesicles by tumor cells Diagnosis [ 112 ] Isomirs of miR-21, miR-375 and miR-204 PCa cells Urine MARCKS, BTG2, PTEN, RECK The miRNA-read-length of miR-204, miR-21 and miR-375 showed clear differences when comparing controls with PCa patient samples. Progression [ 113 , 114 ] miR-141 PCa cells Serum / Exosomal miR-141 is upregulated in the serum from patients with PCa compared with patients with benign prostate hyperplasia or the healthy volunteers Metastasis [ 115 ] miR-200c-3p Urine PCa cells ZEB1, ZEB2, SNAIL2 miRNA re-expression inhibits prostasphere formation, decreases clonogenic survival, and reduces NOTCH1 and LIN28B gene expression, the drivers of self-renewal.…”

Dysregulation of microRNA‑23b‑3p contributes to the development of intracranial aneurysms by targeting phosphatase and tensin homolog

“…P<0.05 was considered to indicate a statistically significance. (20), including non-small cell lung cancer and gastric cancer, by acting on different signaling pathways. the present study aimed to increase our understanding of the association between mir-23b-3p level and ia.…”

Extracellular Vesicles (EVs) and Pancreatic Cancer: From the Role of EVs to the Interference with EV-Mediated Reciprocal Communication

“…Recent evidence suggested that high levels of miRNA-23b-3p are detected in exosomes from PANC-1 cells. In this study, it was investigated that exosome-mediated transfer of miRNA-23b-3p can promote the proliferation, migration and invasion of PANC-1 cells [11] (Figure 1 and Table 1).…”