MiR-345 suppresses proliferation, migration and invasion by targeting Smad1 in human prostate cancer.
01 Jan 2016-Journal of Cancer Research and Clinical Oncology (Springer Berlin Heidelberg)-Vol. 142, Iss: 1, pp 213-224
TL;DR: The data suggest that miR-345 exerts a suppressive effect on prostate cancer proliferation, invasion and migration through downregulation of Smad1.
Abstract: The roles of dysregulated microRNAs in prostate cancer metastasis are still unknown. In this study, we found that the expression of miR-345 was significantly downregulated in prostate cancer and clinical prostate cancer tissues. Overexpression of miR-345 in prostate cancer cells suppressed proliferation, migration and invasion. Using nude mice model, we revealed that miR-345 inhibits the growth of prostate cancer cells in vivo and in vitro. Furthermore, we identified and validated Smad1 as a direct target of miR-345. Ectopic expression of Smad1 without its 3′-UTR rescued miR-345-induced cell migration and invasion inhibition. Taken together, our data suggest that miR-345 exerts a suppressive effect on prostate cancer proliferation, invasion and migration through downregulation of Smad1.
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TL;DR: The relationships of specific microRNAs to certain features and risk factors associated with osteoarthritis such as inflammation, obesity, autophagy, and cartilage homeostasis are reviewed and the potential use of micro RNAs for therapeutic purposes is identified.
Abstract: Micro ribonucleic acid (microRNA) regulation and expression has become an emerging field in determining the mechanisms regulating a variety of inflammation-mediated diseases. Several studies have focused on specific microRNAs that are differentially expressed in cases of osteoarthritis. Furthermore, several targets of these miRNAs important in disease progression have also been identified. In this review, we focus on microRNA biogenesis, regulation, detection, and quantification with an emphasis on cellular localization and how these concepts may be linked to disease processes such as osteoarthritis. Next, we review the relationships of specific microRNAs to certain features and risk factors associated with osteoarthritis such as inflammation, obesity, autophagy, and cartilage homeostasis. We also identify certain microRNAs that are differentially expressed in osteoarthritis but have unidentified targets and functions in the disease state. Lastly, we identify the potential use of microRNAs for therapeutic purposes and also mention certain remedies that regulate microRNA expression.
91 citations
TL;DR: It was found that mTOR/STAT3/AKT pathway and its downstream targets including Slug, Snail and Twist may be involved in IRF1 mediated EMT process and this study highlights the potential effects of miR-345 on prognosis and treatment of HCC.
Abstract: MicroRNAs (miRNAs) have been reported to play critical roles in tumor progression including hepatocellular carcinoma (HCC). Thus, the underlying mechanisms need further investigation. Previous study reported that loss of miR-345 expression indicated a poor prognosis of HCC patients. This study evaluated whether loss of miR-345 could promote the tumor metastasis and epithelial-mesenchymal-transition (EMT) of HCC by targeting interferon regulatory factor 1 (IRF1)-mediated mTOR/STAT3/AKT signaling. Underexpression of miR-345 was identified in 65 cases of human HCC compared to matched tumor-adjacent tissues by qRT-PCR. Moreover, we found that reduced expression of mi-345 was observed in HCC cell lines. The restoration of miR-345 inhibited cell migration and invasion in HCCLM3 cells, while its loss facilitated the cell mobility of HepG2 cells. Furthermore, miR-345 over-expression reduced lung metastases of HCC cells in nude mice. Notably, miR-345 overexpression prohibited, while its knockdown enhanced the EMT process of HCC cell lines in vitro. Bioinformatics software predicted that IRF1 was a direct target of miR-345. We then observed the negative regulation of miR-345 on IRF1 protein expression and the direct binding between them was further verified by dual-luciferase assays in HCC cells. In addition, over-expression of IRF1 mRNA was inversely correlated with the level of miR-345 in HCC specimens. Restoration of IRF1 resulted in promoted EMT and cell mobility in miR-345 overexpressing HCCLM3 cells. It was found that mTOR/STAT3/AKT pathway and its downstream targets including Slug, Snail and Twist may be involved in IRF1 mediated EMT process. In conclusion, miR-345 acts as an inhibitor of EMT process in HCC cells by targeting IRF1 and this study highlights the potential effects of miR-345 on prognosis and treatment of HCC.
65 citations
TL;DR: MiR-199a-3p suppressed proliferation and invasion of PCa cells by targeting Smad1.
Abstract: // Feng Qu 1, 2, * , Jinyu Zheng 3, * , Weidong Gan 1, 2, * , Huibo Lian 1, 2 , Hua He 4 , Wuping Li 4, 5 , Tian Yuan 4 , Yaling Yang 4 , Xiaogong Li 1 , Changwei Ji 1, 2 , Xiang Yan 1, 2 , Linfeng Xu 1, 2 and Hongqian Guo 1, 2 1 Department of Urology, The Affiliated Nanjing Drum Tower Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, 210008, China 2 Institute of Urology, Nanjing University, Nanjing, Jiangsu, 210093, China 3 Department of Pathology, The Affiliated Nanjing Drum Tower Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, 210008, China 4 Department of Hematopathology, Division of Pathology and Laboratory Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas, 77030, USA 5 Department of Lymphoma, Jiangxi Cancer Hospital, Nanchang, Jiangxi, 330029, China * These authors contributed equally to this work Correspondence to: Feng Qu, email: qufeng01@gmail.com Hongqian Guo, email: dr.guohongqian@gmail.com Keywords: MiR-199a-3p, Smad1, prostate cancer, proliferation, invasion Received: February 10, 2017 Accepted: March 10, 2017 Published: April 18, 2017 ABSTRACT Objectives: This study was intended to analyze effects of miR-199a-3p and Smad1 on proliferation, migration and invasion of prostate cancer (PCa) cells. Results: MiR-199a-3p was significantly decreased in PCa tissues in comparison to that in adjacent normal tissues ( P < 0.05). Over-expressed miR-199a-3p markedly suppressed proliferation and invasion of PCa cells ( P < 0.05). MiR-199a-3p was negatively correlated with Smad1 expression, and overexpression of Smad1 could antagonize the effects of miR-199a-3p on PCa cells. Materials and methods: The PCa tissues and their adjacent normal tissues were collected from 54 PCa patients. Expressions of miR-199a-3p and Smad1 mRNA in tissues and cells were evaluated with real-time quantitative polymerase chain reaction (RT-qPCR), and immunohistochemistry assay was used to detect Smad1 protein expressions. The target relationship between miR-199a-3p and Smad1 was assessed by luciferase reporter assay. The PCa cell lines ( i.e. PC-3 cells) were transfected with miR-199a-3p mimics and Smad1-cDNA. MTT and Transwell assays were applied to detect proliferative, migratory and invasive abilities of PCa cells. Conclusions: MiR-199a-3p suppressed proliferation and invasion of PCa cells by targeting Smad1.
39 citations
Cites background from "MiR-345 suppresses proliferation, m..."
...metalloproteinase-2 (MMP-2) and Smad1] [9, 11, 12]....
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...Furthermore, the ALK2/Smad1 pathway activated by endoglin was found to inhibit motility of PCa cells, and down-regulated Smad1 expressions due to target of miR-345 could inhibit growth, invasion and migration of human PCa cells [12, 23]....
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...com/oncotarget hypertrophy based on miRNA microarray analysis [12]....
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...Accumulating evidences have indicated that miRNAs (e.g. miR-182, miR-130b and miR-345) may act as novel modulators for PCa development through regulation of mRNA of specific genes [e.g. metalloproteinase-2 (MMP-2) and Smad1] [9, 11, 12]....
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TL;DR: An integrated analysis of miRNA and gene expression profiles highlighted a functional miRNA-gene regulatory module associated with liver fibrosis, which, to some extent, may provide important clues to better understand the underlying pathogenesis of liver Fibrosis.
39 citations
TL;DR: A novel conceptual framework is provided that overcome the need of performing ex novo identification of suitable reference genes in single experimental systems and identified suitable reference miRNAs for future miRNA expression studies in exosomes plasma and tissues CRC samples.
Abstract: MicroRNAs (miRNAs) hold great promise in cancer research. The use of appropriate reference miRNAs for normalization of qPCR data is crucial for accurate expression analysis. We present here analysis and verification of current data, proposing a workflow strategy for identification of reference miRNAs in colorectal cancer (CRC). We performed a systematic review of studies aimed to identify stable reference miRNAs in CRC through high-throughput screening. Among the candidate miRNAs selected from the literature we excluded those predicted to target oncogenes or tumor suppressor gene. We then assessed the expression levels of the remaining candidates in exosomes, plasma and tissue samples from CRC patients and healthy controls. The expression stability was evaluated by box-plot, ∆Cq analysis, NormFinder and BestKeeper statistical algorithms. The effects of normalisers on the relative quantification of the oncogenic miR-1290 was also assessed. Our results consistently showed that different combinations of miR-520d, miR-1228 and miR-345 provided the most stably expressed reference miRNAs in the three biological matrices. We identified suitable reference miRNAs for future miRNA expression studies in exosomes plasma and tissues CRC samples. We also provided a novel conceptual framework that overcome the need of performing ex novo identification of suitable reference genes in single experimental systems.
39 citations
References
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TL;DR: Although they escaped notice until relatively recently, miRNAs comprise one of the more abundant classes of gene regulatory molecules in multicellular organisms and likely influence the output of many protein-coding genes.
32,946 citations
"MiR-345 suppresses proliferation, m..." refers background in this paper
...Over the past few years, hundreds of miRNAs have been shown to play important roles in regulating gene expression through degradation of target mRNA or repression of target gene translation in a variety of model systems (Bartel 2004)....
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TL;DR: The most recent data on cancer incidence, mortality, and survival from the American Cancer Society (ACS) is presented in this paper, where the authors compare the three major cancer sites in men (lung, prostate, and colon and rectum [colorectum]) and in two major cancers sites in women (breast and colorectal) over a 15-year period.
Abstract: Each year, the American Cancer Society estimates the number of new cancer cases and deaths expected in the United States in the current year and compiles the most recent data on cancer incidence, mortality, and survival based on incidence data from the National Cancer Institute, Centers for Disease Control and Prevention, and the North American Association of Central Cancer Registries and mortality data from the National Center for Health Statistics. Incidence and death rates are standardized by age to the 2000 United States standard million population. A total of 1,479,350 new cancer cases and 562,340 deaths from cancer are projected to occur in the United States in 2009. Overall cancer incidence rates decreased in the most recent time period in both men (1.8% per year from 2001 to 2005) and women (0.6% per year from 1998 to 2005), largely because of decreases in the three major cancer sites in men (lung, prostate, and colon and rectum [colorectum]) and in two major cancer sites in women (breast and colorectum). Overall cancer death rates decreased in men by 19.2% between 1990 and 2005, with decreases in lung (37%), prostate (24%), and colorectal (17%) cancer rates accounting for nearly 80% of the total decrease. Among women, overall cancer death rates between 1991 and 2005 decreased by 11.4%, with decreases in breast (37%) and colorectal (24%) cancer rates accounting for 60% of the total decrease. The reduction in the overall cancer death rates has resulted in the avoidance of about 650,000 deaths from cancer over the 15-year period. This report also examines cancer incidence, mortality, and survival by site, sex, race/ethnicity, education, geographic area, and calendar year. Although progress has been made in reducing incidence and mortality rates and improving survival, cancer still accounts for more deaths than heart disease in persons younger than 85 years of age. Further progress can be accelerated by applying existing cancer control knowledge across all segments of the population and by supporting new discoveries in cancer prevention, early detection, and treatment.
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TL;DR: MiRNA-expression profiling of human tumours has identified signatures associated with diagnosis, staging, progression, prognosis and response to treatment and has been exploited to identify miRNA genes that might represent downstream targets of activated oncogenic pathways, or that target protein-coding genes involved in cancer.
Abstract: MicroRNA (miRNA ) alterations are involved in the initiation and progression of human cancer. The causes of the widespread differential expression of miRNA genes in malignant compared with normal cells can be explained by the location of these genes in cancer-associated genomic regions, by epigenetic mechanisms and by alterations in the miRNA processing machinery. MiRNA-expression profiling of human tumours has identified signatures associated with diagnosis, staging, progression, prognosis and response to treatment. In addition, profiling has been exploited to identify miRNA genes that might represent downstream targets of activated oncogenic pathways, or that target protein- coding genes involved in cancer.
6,345 citations
"MiR-345 suppresses proliferation, m..." refers background in this paper
...Evidence suggests that miRNAs may function as a novel class of both oncogenes and tumor suppressors (Calin and Croce 2006; Xu et al. 2012; Wei et al. 2012; Hou et al. 2011; Josson et al. 2014)....
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Journal Article•
TL;DR: The causes of the widespread differential expression of miRNA genes in malignant compared with normal cells can be explained by the location of these genes in cancer-associated genomic regions, by epigenetic mechanisms and by alterations in the miRNA processing machinery as discussed by the authors.
Abstract: MicroRNA (miRNA) alterations are involved in the initiation and progression of human cancer. The causes of the widespread differential expression of miRNA genes in malignant compared with normal cells can be explained by the location of these genes in cancer-associated genomic regions, by epigenetic mechanisms and by alterations in the miRNA processing machinery. MiRNA-expression profiling of human tumours has identified signatures associated with diagnosis, staging, progression, prognosis and response to treatment. In addition, profiling has been exploited to identify miRNA genes that might represent downstream targets of activated oncogenic pathways, or that target protein- coding genes involved in cancer.
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TL;DR: The number of cancer survivors continues to increase because of both advances in early detection and treatment and the aging and growth of the population and for the public health community to better serve these survivors, the American Cancer Society and the National Cancer Institute collaborate to estimate the number of current and future cancer survivors.
Abstract: The number of cancer survivors continues to increase because of both advances in early detection and treatment and the aging and growth of the population. For the public health community to better serve these survivors, the American Cancer Society and the National Cancer Institute collaborate to estimate the number of current and future cancer survivors using data from the Surveillance, Epidemiology, and End Results cancer registries. In addition, current treatment patterns for the most prevalent cancer types are presented based on information in the National Cancer Data Base and treatment-related side effects are briefly described. More than 15.5 million Americans with a history of cancer were alive on January 1, 2016, and this number is projected to reach more than 20 million by January 1, 2026. The 3 most prevalent cancers are prostate (3,306,760), colon and rectum (724,690), and melanoma (614,460) among males and breast (3,560,570), uterine corpus (757,190), and colon and rectum (727,350) among females. More than one-half (56%) of survivors were diagnosed within the past 10 years, and almost one-half (47%) are aged 70 years or older. People with a history of cancer have unique medical and psychosocial needs that require proactive assessment and management by primary care providers. Although there are a growing number of tools that can assist patients, caregivers, and clinicians in navigating the various phases of cancer survivorship, further evidence-based resources are needed to optimize care. CA Cancer J Clin 2016;66:271-289. © 2016 American Cancer Society.
5,516 citations