Upregulation of miR-194 contributes to tumor growth and progression in pancreatic ductal adenocarcinoma

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal types of human cancer worldwide. In the present study, we investigated the diagnostic and biological significance of microRNA-194 (miR-194) in PDAC. miRNA expression profiling of human PDACs and adjacent normal pancreatic tissues identified a total of 16 genes including miR-194 with >1.15-fold expression changes (8 overexpressed and 8 underexpressed). Quantitative real-time polymerase chain reaction (PCR) revealed elevation of serum miR-194 levels were significantly greater in PDAC patients than in duodenal adenocarcinoma patients and healthy controls. Receiver operating characteristic analysis demonstrated that serum miR-194 had a sensitivity of 54.3% and a specificity of 57.5% for discriminating PDAC patients from healthy controls. Combined analysis of the 3 groups yielded a sensitivity of 84.0 and a specificity of 75.0% for the combined detection of miR-192 and miR-194 in the diagnosis of PDAC. Ectopic expression of miR-194 in PANC-1 pancreatic cancer cells enhanced cell proliferation, migration and colony formation, which was coupled with decreased expression of the tumor suppressor DACH1. miR-194 overexpression increased tumor growth and local invasion and suppressed the expression of DACH1 in an orthotopic pancreatic cancer mouse model. In conclusion, upregulation of miR-194 contributes to tumor growth and progression in PDAC, possibly through suppression of DACH1. However, serum miR-194 has a low capacity for detection of PDAC. Combined detection of serum miR-192 and miR-194 levels may serve as a sensitive diagnostic biomarker for PDAC.

Clinically relevant circulating microRNA profiling studies in pancreatic cancer using meta-analysis

“…Ultimately, there are 29 articles with 36 studies [2, 7–13, 15–35] published between 2009 and 2016 examining the efficacy of miRNAs for diagnosing PaCa compared with healthy controls and included a total of 3843 participants (2225 patients with PaCa and 1618 controls) from the United States, Japan, Germany, France, Denmark, and China, shown in Table 1. Habbe et al's article [12], Que et al's article [23], Cote et al's article [13], Xie et al's article [33], Humeau et al's article [7], Cao et al's article [2] and Xu et al's article [35] included 2 studies, and the remaining 21 articles included 1 study each [8–11, 15–22, 24–32, 34]. Next, we found that 21 studies were performed in Asian populations and the other 15 studies were performed in Caucasian populations.…”

Promotional effect of microRNA-194 on breast cancer cells via targeting F-box/WD repeat-containing protein 7

“…These studies indicated that miR-194 had various target genes (31)(32)(33)(34)(35)(36)(37)(38)(39)(40). Previous studies have demonstrated that miR-194 inhibited cell migration and invasion, which may have contributed to the anti-tumor activity of trastuzumab on HER2-overexpressing breast cancer cells (41,42). Iizuka et al (9) demonstrated that the expression level of miR-194 was increased in human breast cancer cell lines and a rat mammary cancer model induced by radiation.…”

“…The results of the bioinformatic prediction analysis revealed that miR-194 had 367 potential target genes, which may be associated with the numerous functions of miR-194 in a variety of cancer subtypes. According to the ranking results of the bioinformatic analysis and previous studies investigating breast cancer cell proliferation (41,42), the present study focused on the target gene of miR-194, Fbxw-7, which was identified by performing a luciferase assay. Furthermore, the present study demonstrated that miR-194 promoted the proliferation of breast cancer cells by targeting Fbxw-7 and upregulating the expression levels of cyclins D and E. Previous studies revealed that Fbxw-7 acted as a tumor suppressor gene in a number of cancer subtypes (16,43).…”

MiR-194, commonly repressed in colorectal cancer, suppresses tumor growth by regulating the MAP4K4/c-Jun/MDM2 signaling pathway

“…For example, miR-194 was found to act as a tumor suppressor in gastric cancer, 10 endometrial cancer, 11 renal cell carcinoma, 12 lung cancer, 13 and breast cancer, 14 while upregulated as an oncogene in pancreatic cancer. 15 In CRC, miR-194 has been reported to be downregulated in colon tissues 16 and can predict adenoma recurrence. 17 Sundaram 18 found that miR-194 could promote angiogenesis and facilitate tissue repair by targeting thrombospondin-1.…”