Inhibition of miR-92b suppresses nonsmall cell lung cancer cells growth and motility by targeting RECK

microRNAs play critical roles in the progression and metastasis of nonsmall cell lung cancer (NSCLC). miR-92b acts as an oncogene in some malignancies; however, its role in NSCLC remains poorly understood. Here, we found that miR-92b was significantly increased in human NSCLC tissues and cell lines. Inhibition of miR-92b remarkably suppressed cell proliferation, migration, and invasion of NSCLC cells. Reversion-inducing-cysteine-rich protein with kazal motifs (RECK) was identified to be a target of miR-92b. Expression of miR-92b was negatively correlated with RECK in NSCLC tissues. Collectively, miR-92b might promote NSCLC cell growth and motility partially by inhibiting RECK.     

miR-96 downregulates RECK to promote growth and motility of non-small cell lung cancer cells

MicroRNAs play critical roles in the development and progression of non-small cell lung cancer (NSCLC). miR-96 acts as an oncogene in some malignancies, while its role in NSCLC is unclear. Here, we validated that miR-96 was significantly increased in both human NSCLC tissues and cell lines. Inhibition of miR-96 expression remarkably reduced cell proliferation, colony formation, migration, and invasion of NSCLC cells. Reversion-inducing-cysteine-rich protein with kazal motifs (RECK) was identified as a target of miR-96 in NSCLC cells. In addition, the expression of RECK was found to be negatively correlated with the expression of miR-96 in NSCLC tissues. Our data suggest that miR-96 might promote the growth and motility of NSCLC cells partially by targeting RECK.     

MicroRNA 21 promotes glioma invasion by targeting matrix metalloproteinase regulators

Substantial data indicate that microRNA 21 (miR-21) is significantly elevated in glioblastoma (GBM) and in many other tumors of various origins. This microRNA has been implicated in various aspects of carcinogenesis, including cellular proliferation, apoptosis, and migration. We demonstrate that miR-21 regulates multiple genes associated with glioma cell apoptosis, migration, and invasiveness, including the RECK and TIMP3 genes, which are suppressors of malignancy and inhibitors of matrix metalloproteinases (MMPs). Specific inhibition of miR-21 with antisense oligonucleotides leads to elevated levels of RECK and TIMP3 and therefore reduces MMP activities in vitro and in a human model of gliomas in nude mice. Moreover, downregulation of miR-21 in glioma cells leads to decreases of their migratory and invasion abilities. Our data suggest that miR-21 contributes to glioma malignancy by downregulation of MMP inhibitors, which leads to activation of MMPs, thus promoting invasiveness of cancer cells. Our results also indicate that inhibition of a single oncomir, like miR-21, with specific antisense molecules can provide a novel therapeutic approach for “physiological” modulation of multiple proteins whose expression is deregulated in cancer.     

miR-141 suppresses proliferation and motility of gastric cancer cells by targeting HDGF

miR-141 belongs to the miR-200 family, and has been found to be associated with numerous human malignancies; however, its role in gastric cancer (GC) has not been examined in detail. Here, we validated that miR-141 was decreased in GC tissues and cell lines. Forced expression of miR-141 significantly repressed GC cell proliferation and colony formation. Furthermore, miR-141 suppressed in vitro migration and invasion of GC cells. Hepatoma-derived growth factor (HDGF) was confirmed to be a direct target of miR-141 in GC cells. The suppressive effects of miR-141 on GC cell proliferation, colony formation, in vitro migration, and invasion were partially mediated by suppressing HDGF expression. Moreover, the expression of HDGF was negatively correlated with miR-141 in GC tissues. Our data suggest that miR-141 might be associated and plays essential role in GC progression.     

miR-22 suppresses the proliferation and invasion of gastric cancer cells by inhibiting CD151

Gastric cancer (GC) is the second common cause of cancer-related death worldwide. microRNAs (miRNAs) play important roles in the carcinogenesis of GC. Here, we found that miR-22 was significantly decreased in GC tissue samples and cell lines. Ectopic overexpression of miR-22 remarkably suppressed cell proliferation and colony formation of GC cells. Moreover, overexpression of miR-22 significantly suppressed migration and invasion of GC cells. CD151 was found to be a target of miR-22. Furthermore, overexpression of CD151 significantly attenuated the tumor suppressive effect of miR-22. Taken together, miR-22 might suppress GC cells growth and motility partially by inhibiting CD151.     

Retracted: Targeting of SPP1 by microRNA-340 inhibits gastric cancer cell epithelial–mesenchymal transition through inhibition of the PI3K/AKT signaling pathway

Gastric cancer (GC) is a common heterogeneous disease. The critical roles of microRNA-340 (miR-340) in the development and progression of GC were emphasized in accumulating studies. This study aims to examine the regulatory mechanism of miR-340 in GC cellular processes. Initially, microarray technology was used to identify differentially expressed genes and regulatory miRs in GC. After that, the potential role of miR-340 in GC was determined via ectopic expression, depletion, and reporter assay experiments. Expression of secreted phosphoprotein 1 (SPP1), miR-340, phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathway, and epithelial–mesenchymal transition (EMT)-related genes was measured. Moreover, to further explore the function of miR-340 in vivo and in vitro, proliferation, apoptosis, migration, invasion, and tumorigenic capacity were evaluated. SPP1 was a target gene of miR-340 which could then mediate the PI3K/AKT signaling pathway by targeting SPP1 in GC. Furthermore, miR-340 levels were reduced and SPP1 was enriched in GC tissues and cells, with the PI3K/AKT signaling pathway being activated. Inhibitory effects of upregulated miR-340 on SPP1 and the PI3K/AKT signaling pathway were confirmed in vivo and in vitro. Overexpression of miR-340 or the silencing of SPP1 inhibited GC cell proliferation, invasion, migration, and EMT process, but promoted apoptosis of GC cells. Typically, targeting of SPP1 by miR-340 may contribute to the inhibition of proliferation, migration, invasion, and EMT of GC cells via suppression of PI3K/AKT signaling pathway.     

MicroRNA-221 promotes colorectal cancer cell invasion and metastasis by targeting RECK

MicroRNAs (miRNAs) have recently emerged as regulators of metastasis. We provide insight into the behavior of miR-221 in colorectal cancer (CRC) metastasis by showing that miR-221 is significantly upregulated in metastatic CRC cell lines and tissues. miR-221 overexpression enhances, whereas miR-221 depletion reduces CRC cell migration and invasion in vitro and metastasis in vivo. We identify RECK as a direct target of miR-221, reveal its expression to be inversely correlated with miR-221 in CRC samples and show that its re-introduction reverses miR-221-induced CRC invasiveness. Collectively, miR-221 is an oncogenic miRNA which may regulate CRC migration and invasion through targeting RECK.     

miR-96通过RECK促进结直肠癌细胞的迁移和侵袭

目的:研究miRNA-96在结直肠癌转移中的作用及其机制。方法:采用Transwell试验分析结直肠癌Lo Vo细胞的迁移和侵袭能力,采用荧光素报告基因及蛋白免疫印迹试验研究结直肠癌中miR-96的作用靶点。结果:miR-96抑制剂处理后下调miR-96的表达并抑制Lo Vo细胞的迁移和侵袭。荧光素报告基因试验显示RECK是miR-96的作用靶点,且RECK沉默能够部分阻碍miR-96抑制剂所导致的Lo Vo细胞迁移和侵袭减少。结论:miRNA-96可通过作用于RECK促进结直肠癌细胞转移,这可能成为治疗结直肠癌转移的新靶点。     

MicroRNA-135b/CAMK2D Axis Contribute to Malignant Progression of Gastric Cancer through EMT Process Remodeling

There is a continued need for investigating the roles of microRNAs (miRNAs) and their targets on the progression of gastric cancer (GC), especially metastasis. Here, we performed an integrated study to identify dysregulated miRNAs critical for GC development and progression. miR-135b was determined as a promising biomarker for GC. The expression level of miR-135b was increased among GC cell lines, patient tumor tissues, serum samples, and correlation with aggravation of the GC patients. The in vitro functional assays demonstrated overexpression of miR-135b promoted cell proliferation, migration and invasion in GC, while miR-135b inhibition led to the opposite results. CAMK2D was found to be the direct target of miR-135b, serving as a tumor suppressor in GC cells. Based on our and public datasets, we confirmed the attenuation of CAMK2D expression in GC tissues. And, the expression levels of miR-135b and CAMK2D were closely associated with prognosis of GC patients. Ectopic expression of miR-135b resulted in the down-regulation of CAMK2D. Additionally, CAMK2D was a prerequisite for miR-135b to promote GC cells proliferation and migration by regulating the EMT process, which was confirmed by the in vivo experiments. Importantly, in vivo injection of miR-135b antagomir significantly repressed the tumor growth and metastasis of xenograft models, which suggested that the miR-135b antagomir were promising for clinical applications. Taken together, these results indicate that miR-135b/CAMK2D axis drives GC progression by EMT process remodeling, suggesting that miR-135b may be utilized as a new therapeutic target and prognostic marker for GC patients.     

Modulation of MicroRNA-194 and cell migration by HER2-targeting trastuzumab in breast cancer

Trastuzumab, a humanized monoclonal antibody directed against the extracellular domain of the HER2 oncoprotein, can effectively target HER2-positive breast cancer through several mechanisms. Although the effects of trastuzumab on cancer cell proliferation, angiogenesis and apoptosis have been investigated in depth, the effect of trastuzumab on microRNA (miRNA) has not been extensively studied. We have performed miRNA microarray profiling before and after trastuzumab treatment in SKBr3 and BT474 human breast cancer cells that overexpress HER2. We found that trastuzumab treatment of SKBr3 cells significantly decreased five miRNAs and increased three others, whereas treatment of BT474 cells significantly decreased two miRNAs and increased nine. The only change in miRNA expression observed in both cell lines following trastuzumab treatment was upregulation of miRNA-194 (miR-194) that was further validated in vitro and in vivo. Forced expression of miR-194 in breast cancer cells that overexpress HER2 produced no effect on apoptosis, modest inhibition of proliferation, significant inhibition of cell migration/invasion in vitro and significant inhibition of xenograft growth in vivo. Conversely, knockdown of miR-194 promoted cell migration. Increased miR-194 expression markedly reduced levels of the cytoskeletal protein talin2 and specifically inhibited luciferase reporter activity of a talin2 wild-type 3'-untranslated region, but not that of a mutant reporter, indicating that talin2 is a direct downstream target of miR-194. Trastuzumab treatment inhibited breast cancer cell migration and reduced talin2 expression in vitro and in vivo. Knockdown of talin2 inhibited cell migration/invasion. Knockdown of trastuzumab-induced miR-194 expression with a miR-194 inhibitor compromised trastuzumab-inhibited cell migration in HER2-overexpressing breast cancer cells. Consequently, trastuzumab treatment upregulates miR-194 expression and may exert its cell migration-inhibitory effect through miR-194-mediated downregulation of cytoskeleton protein talin2 in HER2-overexpressing human breast cancer cells.     

Allicin suppresses growth and metastasis of gastric carcinoma: the key role of microRNA-383-5p-mediated inhibition of ERBB4 signaling

ABSTRACT

Allicin is a natural product suppressing the progression of gastric carcinoma (GC). In the current study, the mechanism underlying the anti-GC effect of allicin was explored by focusing on the role of miR-383-5p/ERBB4 signaling. Two GC cell lines were treated with allicin and the effects on viability, apoptosis, migration, invasion, and miR-383-5p/ERBB4 activity in the cells were assessed. The interaction between allicin and miR-383-5p was further explored by inhibiting the miR-383-5p level. Allicin suppressed cell viability and induced apoptosis in both GC cell lines. The compound also inhibited migration and invasion of GC cells, which was associated with the up-regulation miR-383-5p and down-regulation of ERBB4. The inhibition of miR-383-5p by specific inhibitor blocked the anti-GC effect of allicin. Our results demonstrated that allicin contributed to the suppressed growth and metastasis potentials in GC cell lines. The effect was accompanied by an increased level of miR-383-5p and subsequent inhibition of ERBB4.     

miR-155靶向SOCS1对骨肉瘤Saos2细胞的增殖、侵袭和迁移能力的影响

目的:探讨microRNA-155(miR-155)对骨肉瘤Saos2细胞增殖、侵袭和迁移的影响以及其作用机制。方法:利用实时荧光定量(qRT-PCR)实验检测miR-155在正常成骨细胞与骨肉瘤Saos2细胞中的表达水平,以及miR-155-mimic、miR-155-inhibitor的转染效率。采用CCK-8实验检测细胞的增殖能力,Transwell实验和划痕实验分别检测Saos2细胞的侵袭和迁移能力,Western blot检测细胞内的STAT3磷酸化水平以及SOCS1表达水平,双荧光素酶报告基因实验进行靶基因验证。结果:miR-155在骨肉瘤Saos2细胞中表达明显高于正常成骨细胞(P0.001)。在分别转染miR-155-mimic和miR-155-inhibitor后,Saos2细胞内miR-155表达水平明显上调和下降(P0.001)。过表达miR-155可促进Saos2细胞增殖、侵袭和迁移,降低SOCS1的蛋白水平,上调STAT3的磷酸化水平,差异均具有统计学意义。相反,降低miR-155水平可抑制Saos2细胞的增殖、侵袭和迁移能力,差异均具有统计学意义。结论:骨肉瘤Saos2细胞中高表达的miR-155可以通过抑制SOCS1表达来激活STAT3信号通路进而促进细胞的增殖、侵袭和迁移,因此,靶向抑制miR-155表达可以作为潜在治疗骨肉瘤的途径。     

环状RNA circMRPS35通过miR-130a-3p/ZNRF3轴调节胃癌细胞的增殖、凋亡、迁移和侵袭

摘要 目的：探讨环状RNA MRPS35（circMRPS35）对胃癌（GC）细胞增殖、凋亡、迁移和侵袭的调控机制。方法：体外培养人GC细胞系（HGC-27、MGC-803、MKN45和AGS）和正常胃上皮GES-1细胞,实时荧光定量PCR（RT-qPCR）检测circMRPS35、miR-130a-3p和锌环指蛋白3（ZNRF3）mRNA表达。另取MGC-803细胞,分为对照组、pc-NC组、pc-circMRPS35组、pc-circMRPS35+miR-NC组、pc-circMRPS35+miR-130a-3p组,采用Lipofectamine 3000进行质粒转染。RT-qPCR检测circMRPS35、miR-130a-3p和ZNRF3 mRNA表达,Western blot检测ZNRF3蛋白表达,CCK-8法、流式细胞术检测细胞增殖与凋亡,划痕实验和Transwell小室实验检测细胞迁移与侵袭能力,裸鼠移植瘤实验探究circMRPS35对GC细胞体内生长的影响。双荧光素酶报告基因检测miR-130a-3p与circMRPS35或ZNRF3的靶标关系。结果：GC细胞系中circMRPS35和ZNRF3 mRNA呈低表达,miR-130a-3p呈高表达（均P＜0.05）。过表达circMRPS35可降低miR-130a-3p,上调ZNRF3 mRNA和蛋白水平,抑制细胞增殖、迁移和侵袭,并促进细胞凋亡（均P＜0.05）;circMRPS35过表达对GC细胞恶性行为和裸鼠移植瘤生长的抑制作用可被miR-130a-3p mimic逆转（P＜0.05）。双荧光素酶实验结果显示,过表达miR-130a-3p可降低circMRPS35-WT和ZNRF3-WT的荧光素酶活性（P＜0.05）。结论：circMRPS35可能通过miR-130a-3p/ZNRF3轴抑制GC细胞的增殖、迁移和侵袭,并促进细胞凋亡。     

CEACAM5 targeted by miR-498 promotes cell proliferation,migration and epithelial to mesenchymal transition in gastric cancer

ObjectiveRecent studies have shown that carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) may serve as an independent predictor of advanced gastric cancer (GC). The purpose of this research is to explore the patterns of expression, functions, and upstream regulatory pathway of CEACAM5 in GC.MethodsThe levels of miR-498 and CEACAM5 expression in GC cells and tissues were measured via qRT-PCR. Wound-healing, CCK-8, and western blotting experiments were conducted for the evaluation of GC cell migration, proliferation, and epithelial-mesenchymal transition (EMT), respectively. The targeting relationship between miR-498 and CEACAM5 was validated via pull-down and luciferase reporter assays. Xenograft tumor mouse models were established to observe CEACAM5’s influence on the growth of tumors in vivo.ResultsElevated levels of CEACAM5 were detected among the GC cells and tissues. The results of the in vitro experiments revealed that the knockdown of CEACAM5 in GC cells significantly inhibited their proliferation, migration, and EMT. Moreover, CEACAM5 inhibition effectively hampered GC cell growth within the nude mice. Moreover, miR-498 directly targeted CEACAM5. MiR-498 downregulation had been observed among the cells and tissues of GC. The stimulation of GC cell proliferation, migration, and EMT, which had been engendered by CEACAM5 overexpression, was reversible through the overexpression of miR-498.ConclusionThe outcomes of this research suggest that miR-498 is capable of repressing the proliferation, migration, and EMT of GC cells through CEACAM5 downregulation.     

The MicroRNA-217 Functions as a Potential Tumor Suppressor in Gastric Cancer by Targeting GPC5

Gastric cancer (GC) is one of the most common malignancies worldwide. Emerging evidence has shown that aberrant expression of microRNAs (miRNAs) plays important roles in cancer progression. However, little is known about the potential role of miR-217 in GC. In this study, we investigated the role of miR-217 on GC cell proliferation and invasion. The expression of miR-217 was down-regulated in GC cells and human GC tissues. Enforced expression of miR-217 inhibited GC cells proliferation and invasion. Moreover, Glypican-5 (GPC5), a new ocncogene, was identified as the potential target of miR-217. In addition, overexpression of miR-217 impaired GPC5-induced promotion of proliferation and invasion in GC cells. In conclusion, these findings revealed that miR-217 functioned as a tumor suppressor and inhibited the proliferation and invasion of GC cells by targeting GPC5, which might consequently serve as a therapeutic target for GC patients.     

microRNA-501-5p promotes cell proliferation and migration in gastric cancer by downregulating LPAR1

In spite of the achievement in treatment, the gastric cancer (GC) mortality still remains high. MicroRNAs (miRNAs) are a group of small noncoding RNAs that play a crucial part in tumor progression. In this study, we explored the expression and function of microRNA-501-5p (miR-501-5p) in GC cell lines. Quantitative real-time polymerase chain reaction assay results suggested that miR-501-5p was significantly upregulated in GC tissues and cell lines. And, the Cell Counting Kit-8 colony formation and cell migration assay results showed that the downregulation of miR-501-5p decreased GC cell proliferation and migration. Besides that, we found that GC cell cycle was arrested in G2 phase and cell apoptosis rate was increased by silencing the expression of miR-501-5p in GC cell lines using the flow cytometry. We also found that miR-501-5p could directly target lysophosphatidic acid receptor 1 (LPAR1) and negatively regulate LPAR1 expression in GC cell lines by performing dual-luciferase reporter gene assay and Western blot analysis. And, LPAR1 was significantly downregulated in GC tissues and inversely correlated with miR-501-5p expression. Furthermore, LPAR1 downregulation promoted cell proliferation and migration, which were attenuated by cotransfection of miR-501-5p inhibitor in GC cells. In conclusion, miR-501-5p can promote GC cell proliferation and migration by targeting and downregulating LPAR1. miR-501-5p/LPAR1 may become a potential therapeutic target for GC treatment.     

miR-340通过靶向GRP78促进结直肠癌细胞凋亡并抑制其增殖、迁移和侵袭

miR-340能够促进癌细胞的增殖和侵袭,但是在结直肠癌中miR-340如何调控癌症的发生与发展鲜有报道.本研究探究miR-340在结直肠癌细胞中的生物学功能和靶基因调控机制.首先通过RT-qPCR检测不同的结直肠癌细胞株中miR-340的表达水平,再利用过表达和抑制miR-340,分别转染COLO-205细胞,以CC...