Serum exosomal microRNA-370-3p and microRNA-196a-5p are potential biomarkers for the diagnosis and prognosis of hepatocellular carcinoma.

INTRODUCTION: Evidence has shown that some microRNAs (miRNAs) play a role in tumorigenesis of hepatocellular carcinoma (HCC). Herein, we aimed to evaluate the diagnostic and prognostic values of serum exosomal miR-370-3p and miR-196a-5p in patients with HCC. MATERIAL AND METHODS: Serum exosomes in 90 HCC patients were extracted and identified. Serum exosomal miR-370-3p and miR-196a-5p expression in HCC patients were detected. The diagnostic value of miR-370-3p and miR-196a- 5p, relationship between miR-370-3p and miR-196a-5p expression and clinicopathological features and prognosis of patients with HCC were analyzed. Relationship between miR-370-3p and miR-196a-5p expression and liver function indices such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBIL) in HCC patients were analyzed. The effects of miR-370-3p and miR-196a-5p on Huh-7 HCC cells' proliferation, invasion and migration were determined. RESULTS: Lower expression of miR-370-3p and higher expression of miR-196a-5p were found in serum exosomes of HCC patients. Serum exosomal miR-370-3p and miR-196a-5p were associated with tumor size, tumor grade and TNM stage as well as prognosis and liver function indices of HCC patients. Overexpressed miR-370-3p or silenced miR-196a-5p suppressed proliferation, invasion and migration of Huh-7 HCC cells. CONCLUSIONS: We suggest that miR-370-3p/miR-196a-5p in serum exosomes of HCC patients could be potential biomarkers for the diagnosis and prognosis of HCC.

Silencing lncRNA LINC01410 suppresses cell viability yet promotes apoptosis and sensitivity to temozolomide in glioblastoma cells by inactivating PTEN/AKT pathway via targeting miR-370-3p.

BACKGROUND: Long non-coding RNAs (LncRNAs) are involved in glioblastoma (GBM), but the role of long intergenic non-protein coding RNA 01410 (lncRNA LINC01410) is poorly understood. METHODS: The expression of LINC01410 in GBM tissues and cells was analyzed. After transfection or temozolomide (TMZ) treatment, the cell viability and apoptosis were detected using cell counting kit-8 assay and flow cytometry. The targeting relationship between LINC01410 and microRNA (miR)-370-3p was confirmed by dual-luciferase reporter assay. Expressions of LINC01410, miR-370-3p and drug resistance- and Phosphatase and Tensin Homolog (PTEN)/AKT pathway-related factors were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. RESULTS: LINC01410 expression was upregulated in GBM, and silencing of LINC01410 decreased cell viability. A slowed decreased trend in cell viability yet an increased half maximal inhibitory concentration (IC50 for TMZ) value and increased expressions of drug resistance-related factors as well as LINC01410 were found in TMZ-resistant GBM cells. Silencing of LINC01410 also decreased the IC50 value yet promoted the sensitivity and apoptosis in TMZ-resistant cells, while upregulating the expression of PTEN and downregulating the phosphorylation of AKT. MiR-370-3p could competitively bind to LINC01410 and its expression was decreased in both parental and TMZ-resistant GBM cells. Downregulation of miR-370-3p reversed the effects of LINC01410 silencing on cell viability, apoptosis and the expressions of miR-370-3p and PTEN/AKT pathway-related factors. CONCLUSION: Silencing of LINC01410 inhibits cell viability yet enhances apoptosis and sensitivity to TMZ in GBM cells by inactivating PTEN/AKT pathway via targeting miR-370-3p.

Circ_002117 binds to microRNA-370 and promotes endoplasmic reticulum stress-induced apoptosis in gastric cancer.

BACKGROUND: Mounting evidence implicates circular RNAs (circRNAs) in various biological processes during cancer progression. Gastric cancer is a main cause of cancer-related deaths worldwide. Herein, we aimed at investigating whether circ_002117 mediates gastric cancer progression through endoplasmic reticulum (ER) stress. METHODS: Bioinformatics analysis detected differentially expressed circRNAs and their target miRNA candidates, and RT-qPCR was performed to detect expression of circ_002117, microRNA (miRNA)-370 and HERPUD1 in gastric cancer tissues and cells. Gastric cancer cells were transfected with plasmids and their proliferative ability and apoptosis were detected with gain- and loss-of-function assay. The ER of treated cells was observed under a transmission electron microscope. Dual-luciferase reporter gene assay and RIP were performed to detect the interaction between HEPRUD1, miR-370 and circ_002117-treated cells were injected into mice to establish xenograft tumor model. RESULTS: Circ_002117 and HEPRUD1 were poorly expressed whereas miR-370 was highly expressed in clinical cancer tissues and cells. Circ_002117 was indicated to target and suppress miR-370 expression, while HERPUD1 was directly targeted by miR-370. Circ_002117 overexpression or miR-370 deficiency promoted ER stress-induced apoptosis and decreased proliferation of gastric cancer cells, which was reversed by silencing of HEPRUD1. Circ_002117 overexpression or miR-370 depletion significantly suppressed gastric cancer tumorigenesis in vivo. CONCLUSIONS: Taken altogether, circ_002117 facilitated ER stress-induced apoptosis in gastric cancer by upregulating HERPUD1 through miR-370 inhibition.

The miR-370/UQCRC2 axis facilitates tumorigenesis by regulating epithelial-mesenchymal transition in Gastric Cancer.

Ubiquinol-cytochrome c reductase core protein 2 (UQCRC2) is an important mitochondrial complex III subunit. This study investigated the role of UQCRC2 in gastric cancer (GC) and its upstream regulatory microRNAs (miRNAs). UQCRC2 expression levels were lower in GC tissues than non-carcinoma tissues. Furthermore, UQCRC2 levels were negatively correlated with lymph node metastasis, relapse, and tumor grade. Bioinformatics analysis predicted UQCRC2 as the target gene for miR-370, and this was verified in luciferase reporter assays. MiR-370 levels were inversely correlated with UQCRC2 levels in GC. UQCRC2 overexpression suppressed GC cell migration and invasion in vitro and in vivo, whereas up-regulating miR-370 reversed these effects. Western blotting analysis showed that miR-370 targeted UQCRC2 and positively regulated the epithelial-mesenchymal transition (EMT) signaling pathway in GC cells. Therefore, the miR-370/UQCRC2 axis may regulate EMT signaling pathways to affect tumor proliferation and metastasis and is, thus, a potential target for GC treatment.

circRNA_001275 upregulates Wnt7a expression by competitively sponging miR­370­3p to promote cisplatin resistance in esophageal cancer.

Circular RNAs (circRNAs) are aberrantly expressed in various tumors and are associated with tumorigenesis. The present study aimed to determine the role of circRNA_001275 in cisplatin­resistant esophageal cancer. Three pairs of cisplatin­resistant tissues and corresponding adjacent tissues were collected and subjected to circRNA chip analysis. Additionally, the effect of circRNA_001275 on cisplatin­resistant cells was investigated. The relationship between circRNA_001275, microRNAs (miRs) and target genes were analyzed using luciferase assays, and validated via reverse transcription­quantitative PCR (RT­qPCR) and western blotting. The results showed that circRNA_001275 was significantly upregulated in cisplatin­resistant esophageal cancer tissues and cells (P<0.05). Overexpression of circRNA_001275 promoted the proliferation and invasion, and decreased the apoptosis of cisplatin­resistant cells. On the other hand, circRNA_001275 silencing inhibited cell proliferation and invasion, and promoted cell apoptosis (P<0.05). Dual­luciferase reporter assays revealed that circRNA_001275 directly binds to miR­370­3p, and that Wnt family member 7A (Wnt7a) is targeted by miR­370­3p. RT­qPCR and western blotting further demonstrated that circRNA_001275 serves as an miR­370­3p sponge to upregulate Wnt7a expression. In conclusion, the present study revealed that circRNA_001275 was upregulated in cisplatin­resistant esophageal cancer and promoted cisplatin resistance by sponging miR­370­3p to upregulate Wnt7a expression. Therefore, circRNA_001275 may serve as a potential diagnostic biomarker and therapeutic target for patients with cisplatin­resistant esophageal cancer.

Silencing of KCNK15-AS1 inhibits lung cancer cell proliferation via upregulation of miR-202 and miR-370.

Lung cancer is the most common cause of cancer-associated mortality globally. Long non-coding RNAs (lncRNAs) are transcripts with a length of >200 nucleotides, which are not translated into proteins. Growing evidence has indicated that certain lncRNAs are associated with various biological processes in cancer. However, the functions of KCNK15 and WISP2 antisense RNA 1 (KCNK15-AS1) in lung cancer carcinogenesis and progression have remained elusive. The present study indicated that KCNK15-AS1 was overexpressed in lung adenocarcinoma tissues compared with paracancerous normal tissues, and the high expression of KCNK15-AS1 was significantly associated with poor prognosis compared with the patients with low expression (P<0.001). Furthermore, the knockdown of KCNK15-AS1 was performed in A549 and H460 lung cancer cells with small interfering RNA, resulting in a significant inhibition of the proliferation, a decrease in the mRNA and protein expression of cyclin D1 (CCND1) and epidermal growth factor receptor (EGFR), in addition to the phosphorylation of protein kinase B, with a concomitant increase in the expression of microRNA (miR)-202 and miR-370 compared with negative control group. Rescue experiments demonstrated that the inhibition of miR-202 or miR-370 partially recovered the EGFR and CCND1 expression and the proliferation rates, which were reduced by KCNK15-AS1 silencing. In conclusion, these results suggested that KCNK15-AS1 functions as an oncogene via regulating the miR-202/miR-370/EGFR axis in lung cancer and may provide a potential target for lung cancer treatment.

miR-370 inhibits the oxidative stress and apoptosis of cardiac myocytes induced by hydrogen peroxide by targeting FOXO1.

Myocardial infarction, one of the main factors that threatens human health, leads to cardiac cell death. Myocardial cells suffer ischemia and hypoxia for a long period of time, which can lead to irreversible cell death or apoptosis and cardiac dysfunction. MicroRNAs (miRs) have been reported to play an important role in a wide range of biological processes in cardiac myocytes, which respond to inflammation and oxidative stress. The aim of the present study was to investigate the effect of miR-370 on oxidative stress and apoptosis of cardiac myocytes in ischemic H9C2 cells induced by hydrogen peroxide (H2O2). H9C2 cells were cultured and treated with different concentrations of H2O2 solution. Then, cells were transfected with miR-370 mimic or negative control (NC) mimic, small interfering (si)-RNA-Forkhead box O1 (FOXO1) and NC siRNA. A Cell Counting Kit-8 and flow cytometry assay were conducted to detect cell viability and cell apoptosis. The expression of oxidative stress associated factors were detected by ELISA. The levels of miR-370 and FOXO1 were examined using western blotting and reverse transcription-quantitative PCR. A luciferase reporter gene assay was performed to verify whether FOXO1 was a target gene of miR-370. The results revealed that miR-370 expression was downregulated and FOXO1 expression was increased in H9C2 cells induced by H2O2. Additionally, FOXO1 was proven to be a target of miR-370. The ELISA and flow cytometry assay revealed that miR-370 overexpression and FOXO1 silencing reversed H2O2-induced oxidative stress and apoptosis. The results indicated that miR-370 could inhibit the oxidative stress and apoptosis of H9C2 cells induced by H2O2 by targeting FOXO1. Therefore, miR-370 may be a new therapeutic target for ischemic heart disease.

The protective effect of bone marrow-derived mesenchymal stem cells in liver ischemia/reperfusion injury via down-regulation of miR-370.

OBJECTIVES: Liver transplantation is the most important therapy for end-stage liver disease and ischemia reperfusion (I/R) injury is indeed a risk factor for hepatic failure after grafting. The role of miRNAs in I/R is not completely understood. The aim of this study was to investigate the potential protective role of the mesenchymal stem cells (MSCs) and ischemic preconditioning on miR-370 expression and tissue injury in hepatic I/R injury. MATERIALS AND METHODS: In this study, 24 BALB/c mice were divided into 4 groups, including sham, I/R, I/R mouse that received MSCs (I/R+MSC) and ischemia preconditioning (IPC) The expression levels of hepatic miR-370, Bcl2 and BAX in male BALB/c mice in different groups including hepatic I/R, hepatic I/R received MSCs, and hepatic I/R with IPC were assessed by quantitative real-time PCR. The effect of miR-370 on hepatic I/R was investigated by serum liver enzyme analysis and histological examination. RESULTS: The expression of miR-370 was significantly up-regulated in the mice subjected to hepatic I/R injury as compared with the sham operated mice. Injection of MSCs led to the down-regulation of the serum liver enzymes, expression of miR-370 and BAX, up-regulation of Bcl2 as well as the improvement of hepatic histological damage. IPC led to similar results, but the difference was not significant. CONCLUSION: Our data suggest that miR-370 affected the Blc2/BAX pathway in hepatic I/R injury, and down- regulation of miR-370 by BM-MSCs efficiently attenuated the liver damage.

MicroRNA-370 protects against myocardial ischemia/reperfusion injury in mice following sevoflurane anesthetic preconditioning through PLIN5-dependent PPAR signaling pathway.

Myocardial ischemia/reperfusion injury (IRI) has long been identified to be a contributor to adverse cardiovascular outcomes following myocardial ischemia, cardiac surgery or circulatory arrest. This study aims to investigate the effects of microRNA (miR-370) targeting perilipin-5 (PLIN5) in mice following sevoflurane anesthetic preconditioning (SAP). A mouse model of left ventricular myocardial IRI was established, followed by the evaluation of myocardial infarction size and cardiac function to determine the effects of SAP. The underlying regulatory mechanisms of miR-370 were analyzed in concert with the treatment of miR-370 mimic, miR-370 inhibitor, or siRNA against PLIN5 in cardiomyocytes isolated from mice with IRI. Also, cardiomyocyte proliferation, cell cycle distribution and apoptosis were evaluated following treatment. Lastly, SAP-treated I/R mice were injected with miR-370 inhibitor to verify the mechanism of SAP. The use of SAP conferred cardioprotective effects on myocardial IRI. MiR-370 was downregulated in mice that exhibited IRI, but SAP elevated the miR-370 expression. Functionally, miR-370 negatively targeted PLIN5 and activated the peroxisome proliferator activated-receptor (PPAR) signaling pathway, leading to decreased PPARγ expression but increased PPARα expression. The results also showed that elevation of miR-370 or the silencing of PLIN5 promoted cardiomyocyte proliferation. miR-370 also inhibited cardiomyocyte apoptosis as reflected by decreased caspase-3 expression and increased Bcl-2 expression. Additionally, SAP also alleviated I/R injury by inhibiting PPARγ. This study demonstrates that SAP induces miR-370 and exerts cardioprotective effects on myocardial IRI, where upregulation of miR-370 alleviates myocardial IRI via inhibiting the PLIN5-dependent PPAR signaling pathway.

Effect of microRNA-370 on coronary atherosclerosis and its underlying mechanism.

As a global health problem, cardiovascular disease threatens the lives of human beings. It has been reported that microRNAs (miRs) are important in regulating coronary atherosclerosis. In the present study, the expression levels of miR-370 in peripheral blood mononuclear cells of patients with coronary atherosclerosis were significantly increased compared with healthy patients, as demonstrated by reverse transcription-quantitative polymerase chain reaction analysis. Additionally, the target of miR-370 was predicted as Forkhead Box 1 (FOXO1) with bioinformatics, and was confirmed by a dual luciferase assay. The mRNA and protein expression levels of FOXO1 were inhibited by miR-370. Furthermore, the invasion and proliferation of human umbilical vein endothelial cells were promoted by miR-370 via inhibiting the expression of FOXO1. The results obtained in the present study demonstrated that miR-370 served an important role in regulating coronary atherosclerosis via targeting FOXO1. The present data also indicated that miR-370 may be a promising molecular target for treating coronary atherosclerosis.

Effects of microRNA-370 on mesangial cell proliferation and extracellular matrix accumulation by binding to canopy 1 in a rat model of diabetic nephropathy.

As one major diabetic complication, diabetic nephropathy (DN) has been reported to be associated with various kinds of microRNA (miRNA). Thus, we conducted this study to explore the potential of miR-370 in a rat model of DN through investigation of mesangial cell proliferation and extracellular matrix (ECM). A total of 40 healthy adult male Sprague-Dawley rats were enrolled and assigned into normal (n = 10) and DN ( n = 30, DN rat model) groups. Dual-luciferase reporter assay was performed for the targeting relationship between miR-370 and canopy 1 (CNPY1). Mesangial cells were collected and transfected with prepared mimic, inhibitor or small interfering RNA (siRNA) for analyzing the effect of miR-370 on DN mice with the help of expression and cell biological processes detection. CNPY1 was confirmed as a target gene of miR-370. DN mice had increased expression of miR-370, fibronectin, type I collagen (Col I), type IV collagen (Col IV), and plasminogen activator inhibitor-1 (PAI-1) but reduced CNPY1 expression. Cells transfected with miR-370 mimic and siRNA-CNPY1 had increased expression of fibronectin, Col I, Col IV, and PAI-1 but decreased CNPY1 expression. The miR-370 mimic and siRNA-CNPY1 groups showed increased cell proliferation, as well as elevated ECM accumulation and declined cell apoptosis rate as compared with the blank and negative control groups, with reverse trends observed in the miR-370 inhibitor group. Our study concludes that overexpression of miR-370 promotes mesangial cell proliferation and ECM accumulation by suppressing CNPY1 in a rat model of DN.

MicroRNA-370 inhibits the proliferation, invasion and EMT of gastric cancer cells by directly targeting PAQR4.

It has been reported that PAQR4 (Progestin and AdipoQ Receptor 4) expression is closely associated with progression of many cancers and microRNA (miRNA) processing. However, the effects and its precise mechanisms of PAQR4 in gastric cancer (GC) have not been well clarified. Our study aimed to explore the interaction between PAQR4 and miR-370 in GC. In our study, we found that the miR-370 level was significantly down-regulated in GC tissues and cell lines, and the expression of PAQR4 was dramatically increased. Interestingly, the low miR-370 level was closely associated with up-regulated PAQR4 expression in GC tissues. Moreover, introduction of miR-370 dramatically suppressed proliferation, invasion and EMT of GC cells. Whereas, miR-370 knockdown increased the proliferation, invasion and EMT in GC cells. We demonstrated that miR-370 could directly target PAQR4 by using both bioinformatics analysis and luciferase reporter assay. In addition, PAQR4 silencing had the similar effects with miR-370 overexpression on GC cells. Overexpression of PAQR4 in GC cells partially reversed the inhibitory effects of miR-370 mimic. miR-370 inhibited cell proliferation, invasion and EMT of GC cells by directly down-regulating PAQR4 expression, and miR-370 targeting PAQR4 was responsible for inhibition of the proliferation, invasion and EMT of GC cells.

Long noncoding RNA H19 promotes transforming growth factor-ß-induced epithelial-mesenchymal transition by acting as a competing endogenous RNA of miR-370-3p in ovarian cancer cells.

Ovarian cancer is a gynecological malignant tumor with a high mortality rate among women, owing to metastatic progression and recurrence. Acquisition of invasiveness is accompanied by the loss of epithelial features and a gain of a mesenchymal phenotype, a process known as epithelial-mesenchymal transition (EMT). Transforming growth factor-ß (TGF-ß) has been implicated in the regulation of EMT. In the present study, we aimed to investigate the role of long noncoding RNA H19 and microRNA-370 (miR-370-3p) in TGF-ß-induced EMT. Ovarian cancer cell lines SKOV-3 and OVCAR3 were incubated with different concentrations of TGF-ß, and the results showed that TGF-ß treatment upregulated H19 and downregulated miR-370-3p. In addition, an H19 knockdown or miR-370-3p overexpression suppressed TGF-ß-induced EMT, while H19 overexpression or a miR-370-3p knockdown promoted TGF-ß-induced EMT. Mechanistically, H19 could directly bind to miR-370-3p and effectively act as its competing endogenous RNA. Furthermore, we demonstrated that this activity of H19 was involved in its promotion of TGF-ß-induced EMT. Thus, our results may provide novel insights into the process of TGF-ß-induced EMT.

MicroRNA-370 suppresses the progression and proliferation of human astrocytoma and glioblastoma by negatively regulating ß-catenin and causing activation of FOXO3a.

Certain microRNAs (miRs) regulate the progression and metastasis of various cancer types. In the present study, the role of miR-370 in the progression and proliferation of human astrocytoma and glioblastoma cells was assessed and the underlying molecular mechanism was investigated. miR-370 levels in clinical specimens of human glioma and peritumoral tissues were determined by reverse-transcription quantitative PCR. Oligonucleotide mimics and inhibitors were transfected into the U-251MG human astrocytoma cell line and the and U-87MG glioblastoma cell line and the cell viability of was determined by an MTT assay. The expression of ß-catenin and forkhead box protein (FOX)O3a was determined by western blot analysis. The results revealed that the expression of miR-370 in human glioma tissues was significantly decreased compared with that in peritumoral tissues. The miR-370 levels in patients with grade III/IV gliomas were significantly decreased compared with those in grade I/II. Transfection with miR-370 mimics inhibited the proliferation of U-251MG and U-87MG cells. Furthermore, the miR-370 levels were negatively correlated with ß-catenin and positively correlated with nuclear FOXO3a. In conclusion, miR-370 inhibited the proliferation of human glioma cells by regulating the levels of ß-catenin and the activation of FOXO3a, suggesting that miR-370 was a tumor suppressor in the progression of human astrocytoma and glioblastoma cells.

Glucagon-like peptide-1 effects lipotoxic oxidative stress by regulating the expression of microRNAs.

Aim to confirm whether the treatment of GLP-1 can modulated body weight, lipid metabolism, insulin content, pancreas oxidative stress, improved T-AOC, MDA levels related to FFA-Induced oxidative stress in C57BL/6 mice and INS-1 cells. In this study, GLP-1 makes the expression of AMPK, PPARα, CPT1A and SIRT1 increased, and the expression of SREBP1c, miR-33 and miR-370 decreased. Interestingly, the effects of GLP-1 were less dose dependent as GLP-1 regulated the FFA, which related to gene expression at much lower doses (3 µg/kg, 10 mM, mice and INS-1 respectively) and effects were relatively maintained at higher dose (30 µg/kg, 100 mM, mice and INS-1 respectively) as well. Subsequently, the analysis showed that inhibited expression of miR-33 and miR-370 upregulated the expression of CPT1A and SIRT1, reversely mimics. These results demonstrated for the first time that GLP-1 improve lipotoxic oxidative stress of pancreas by regulate expression of microRNAs.

Upregulation of microRNA-370 facilitates the repair of amputated fingers through targeting forkhead box protein O1.

Angiogenesis is critical to the success of digital replantation. Recent study suggests an important regulatory role of microRNA-370 (miR-370) in ischemia-reperfusion injury. However, its function in digital replantation is poorly understood. In this study, we reported that the expression of miR-370 was upregulated in replantation tissues. miR-370 mimic transfection promoted human umbilical vein endothelial cells (HUVECs) proliferation by regulating the cell cycle and inhibited apoptosis. miR-370 mimic transfection also significantly increased HUVECs migration and induced the formation of capillary-like structures in HUVECs, indicated that miR-370 promoted capillary tube formation in vitro. Furthermore, forkhead box protein O1 (FOXO1) was identified as the functional target of miR-370 by dual-luciferase reporter assay. FOXO1 overexpression vector lacked 3'-UTR together with miR-370 mimic transfection strongly abrogated miR-370-induced cell proliferation and the formation of capillary-like structures in HUVECs. Taken together, our results revealed that the upregulation of miR-370 might facilitate the repair of amputated fingers by regulating angiogenesis through targeting FOXO1. This study provided a potential therapeutic target for the restoration of finger function after replantation.

High MicroRNA-370 Expression Correlates with Tumor Progression and Poor Prognosis in Breast Cancer.

PURPOSE: Deregulation of microRNA-370 (miR-370) has been reported in various cancers, in which it can act as either an oncogene or a tumor suppressor gene. However, the clinicopathologic significance of miR-370 expression in breast cancer has not been studied. METHODS: The expression of miR-370 was determined with quantitative real-time polymerase chain reaction in 60 formalin-fixed, paraffin-embedded primary breast cancer tissues. Additionally, the protein expression levels of previously known targets of miR-370, such as FOXM1, FOXO1, and FOXO3a, were detected using immunohistochemistry. Finally, we analyzed its correlation with target protein expression, clinicopathologic features, and clinical outcome. RESULTS: High levels of miR-370 expression correlated with lymph node metastasis (p=0.009), advanced stage (p=0.002), and frequent perineural invasion (p=0.042). Moreover, patients with high miR-370 expression had poor disease-free survival compared with the low-expression group. However, no correlation was observed between miR-370 and its target protein expression. CONCLUSION: Our results indicate that upregulation of miR-370 in breast cancer is correlated with breast cancer progression and that it might be a potential biomarker for predicting clinical outcomes.

A role of microRNA-370 in hepatic ischaemia-reperfusion injury by targeting transforming growth factor-ß receptor II.

BACKGROUND & AIMS: MicroRNAs (miRNAs) are a group of small non-coding RNAs with modulator activity of gene expression. The role of miRNAs in hepatic ischaemia-reperfusion (IR) injury is currently largely unknown. The aim of this study was to investigate the potential role of miR-370 in hepatic IR injury. METHODS: The expression levels of hepatic miR-370 in male C57BL/6 mice subjected to hepatic IR injury or ischaemia preconditioning were assessed by quantitative real-time PCR. The effect of miR-370 on hepatic IR injury was investigated by serum enzyme analysis and histological examination of liver following treatment of mice with antagomir-370 or control. The levels of proinflammatory cytokines and apoptosis- and proliferation-related genes were also determined by quantitative real-time PCR. Furthermore, the potential targets of miR-370 in this injury were studied by bioinformatics analysis, luciferase assays, quantitative real-time PCR and Western blot. RESULTS: The results showed that miR-370 expression was significantly upregulated in the mice subjected to hepatic IR injury as compared with the sham-operated mice. Inhibition of miR-370 led to the downregulation of serum aminotransferase and proinflammatory cytokines, as well as the improvement of hepatic histological damage. Reporter assays confirmed that miR-370 directly targeted the 3' untranslated region of transforming growth factor-ß receptor II (TßRII). Inhibition of miR-370 was sufficient to reinstate the expression of TßRII and its downstream target phosphorylated Smad3. CONCLUSION: Our data suggest that miR-370 acting via TßRII might play a potential role in hepatic IR injury, and inhibition of miR-370 efficiently attenuated the damage to the liver.

Serum MicroRNA-370 as a potential diagnostic and prognostic biomarker for pediatric acute myeloid leukemia.

BACKGROUND: Controversial data on the expression pattern of microRNA-370 (miR-370) in acute myeloid leukemia (AML) were previously reported. OBJECTIVE: To clarify the expression pattern of miR-370 and its clinical implications in pediatric AML patients. METHODS: Real-time quantitative PCR was performed to detect the expression of miR-370 in both bone marrow mononuclear cells and sera obtained from pediatric AML patients and healthy controls. RESULTS: Compared with healthy controls, the expression levels of miR-370 in the bone marrow and sera of pediatric AML patients were both decreased significantly (both P=0.001). Importantly, serum miR-370 level could efficiently screen pediatric AML patients from healthy controls (Area under receiver operating characteristic curve, AUC =0.993). Then, low serum miR-370 level was significantly associated with French-American-British (FAB) classification subtype M7 subtype (P=0.02) and unfavorable karyotype (P=0.01). Moreover, pediatric AML patients with low serum miR-370 level had shorter relapse-free and overall survivals than those with high serum miR-370 level (both P=0.001). Multivariate analysis further identified serum miR-370 level as an independent prognostic factor for both relapse-free and overall survivals. Interestingly, the prognostic relevance of serum miR-370 level was more obvious in the subgroup of patients with intermediate-risk cytogenetics. CONCLUSIONS: MiR-370 expression may be markedly and consistently decreased in pediatric AML patients and in turn contributes to aggressive progression of this malignancy. Serum miR-370 may serve as a potential non-invasive diagnostic/prognostic marker for pediatric AML patients.

High MicroRNA-370 Expression Correlates with Tumor Progression and Poor Prognosis in Breast Cancer / 한국유방암학회지

PURPOSE: Deregulation of microRNA-370 (miR-370) has been reported in various cancers, in which it can act as either an oncogene or a tumor suppressor gene. However, the clinicopathologic significance of miR-370 expression in breast cancer has not been studied. METHODS: The expression of miR-370 was determined with quantitative real-time polymerase chain reaction in 60 formalin-fixed, paraffin-embedded primary breast cancer tissues. Additionally, the protein expression levels of previously known targets of miR-370, such as FOXM1, FOXO1, and FOXO3a, were detected using immunohistochemistry. Finally, we analyzed its correlation with target protein expression, clinicopathologic features, and clinical outcome. RESULTS: High levels of miR-370 expression correlated with lymph node metastasis (p=0.009), advanced stage (p=0.002), and frequent perineural invasion (p=0.042). Moreover, patients with high miR-370 expression had poor disease-free survival compared with the low-expression group. However, no correlation was observed between miR-370 and its target protein expression. CONCLUSION: Our results indicate that upregulation of miR-370 in breast cancer is correlated with breast cancer progression and that it might be a potential biomarker for predicting clinical outcomes.