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Data are presented as the mean of triplicate experiments. The growth inhibitory effect of the miR-199a-3p and miR-34a mimics was time-dependent, with the maximum inhibition detected 7 days after transfection. Significant difference (P<0.01)
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MicroRNAs (MiRNAs) are small non-coding RNAs (18-25nt) that regulate gene expression mainly through affecting post-transcriptional modification. Osteosarcoma is an aggressive sarcoma of the bone characterized by a high level of genetic instability and recurrent DNA deletions and amplifications. microRNAs (miRNAs) play an important role in cancer ce...
Citations
... Some studies showed a loss of miR-199a/b-3p expression in aggressive breast cancer [44]; other evidence demonstrated the ability of miR-199a/b-3p to inhibit proliferation, migration, and multi-drug resistance. miR-199a/b-3p seems to be down-expressed in many types of cancer [45][46][47][48][49][50][51][52]. According to Shou-Qing Li et al., PAK4 could be a possible target of miR-199a/b-3p with an oncosuppresive role: in human breast cell lines, ectopic expression of miR-199a/b-3p blocks the PAK4/MEK/ERK pathway to inhibit breast cancer progression by inducing G1 phase arrest [52]. ...
Background:
The aim of this study is to identify miRNAs able to predict the outcomes in breast cancer patients after neoadjuvant chemotherapy (NAC).
Patients and methods:
We retrospectively analyzed 24 patients receiving NAC and not reaching pathologic complete response (pCR). miRNAs were analyzed using an Illumina Next-Generation-Sequencing (NGS) system.
Results:
Event-free survival (EFS) and overall survival (OS) were significantly higher in patients with up-regulation of let-7a-5p (EFS p = 0.006; OS p = 0.0001), mirR-100-5p (EFS s p = 0.01; OS p = 0.03), miR-101-3p (EFS p = 0.05; OS p = 0.01), and miR-199a-3p (EFS p = 0.02; OS p = 0.01) in post-NAC samples, independently from breast cancer subtypes. At multivariate analysis, only let-7a-5p was significantly associated with EFS (p = 0.009) and OS (p = 0.0008).
Conclusion:
Up-regulation of the above miRNAs could represent biomarkers in breast cancer.
... Osteosarcoma is the 8 th leading tumor with approximately incidence of 4.4 per one million. Osteosarcoma mostly occurs in adolescents and children, contributing to about 5% of all childhood malignancies and about 9% of tumor-correlated deaths in children [1][2][3][4]. Clinical results illustrated that this cancer has an uncertain prognosis, even with comprehensive therapies including chemotherapy and amputation [3,5,6]. Extensive cancer-associated specific mediators and signaling pathways have been identified in osteosarcoma prognosis, pathogenesis and progression [7][8][9][10]. ...
Growing studies noted that lncRNA was closely related with the initiation and progression of tumors. However, the role of BCRT1 in the progression of osteosarcoma remains unknown. We noted that BCRT1 is significantly upregulated in osteosarcoma specimens and cells. Elevated expression of BCRT1 promotes cell growth and cell cycle in osteosarcoma cell. Moreover, BCRT1 induces EMT and secretion of inflammatory mediators in osteosarcoma cell. We illustrated that elevated expression of BCRT1 decreases miR-1303 expression in MG-63 cell. The expression of miR-1303 is lower in osteosarcoma specimens than in non-tumor specimens. There is an inverse interrelation between miR-1303 levels and BCRT1 levels in osteosarcoma specimens. Furthermore, we identified FGF7 is one direct target gene of miR-1303 in osteosarcoma cell. Ectopic expression of miR-1303 suppresses FGF7 expression and elevated expression of BCRT1 enhanced FGF7 expression in MG-63 cell. Finally, we illustrated that BCRT1 induces osteosarcoma cell cycle and proliferation and promotes EMT progression and inflammatory mediators secretion via modulating FGF7 expression. Our study suggested that BCRT1 acts as one oncogene in osteosarcoma progression.
... Several comprehensive reviews have been written to summarize the involvement of miRNAs in OS (10)(11)(12)(13)(14)(15)(16)(17)(18). Major findings in OS miRNA studies include suggested or experimentally demonstrated oncogenicor metastasis-promoting roles for miR-17-92 cluster (19)(20)(21), miR-181 family (22)(23)(24), miR-27a (23), and miR-21 (25,26) as well as tumor-suppressive roles for miR-15/16 family members (23) and miR-34 (20,27,28). The roles of other miRNAs are less clear, such as the miR-29 family with reports of both elevated and decreased expression in osteosarcoma cell lines and tumors compared to "normal" controls for each sample type (20,21,23,24). ...
MicroRNAs (miRNA) are small non-coding RNA molecules involved in post-transcriptional gene regulation. Deregulation of miRNA expression occurs in cancer, and miRNA expression profiles have been associated with diagnosis and prognosis in many cancers. Osteosarcoma (OS), an aggressive primary tumor of bone, affects ~10,000 dogs each year. Though survival has improved with the addition of chemotherapy, up to 80% of canine patients will succumb to metastatic disease. Reliable prognostic markers are lacking for this disease. miRNAs are attractive targets of biomarker discovery efforts due to their increased stability in easily obtained body fluids as well as within fixed tissue. Previous studies in our laboratory demonstrated that dysregulation of genes in aggressive canine OS tumors that participate in miRNA regulatory networks is reportedly disrupted in OS or other cancers. We utilized RT-qPCR in a 384-well-plate system to measure the relative expression of 190 miRNAs in 14 canine tumors from two cohorts of dogs with good or poor outcome (disease-free interval >300 or <100 days, respectively). Differential expression analysis in this subset guided the selection of candidate miRNAs in tumors and serum samples from larger groups of dogs. We ultimately identified a tumor-based three-miR Cox proportional hazards regression model and a serum-based two-miR model, each being able to distinguish patients with good and poor prognosis via Kaplan–Meier analysis with log rank test. Additionally, we integrated miRNA and gene expression data to identify potentially important miRNA–mRNA interactions that are disrupted in canine OS. Integrated analyses of miRNAs in the three-miR predictive model and disrupted genes from previous expression studies suggest the contribution of the primary tumor microenvironment to the metastatic phenotype of aggressive tumors.
... Moreover, previous studies have pivoted on different miRNAs to explore their specific roles in KOA with the conclusion that the expression of miR-140 and miR-130a is decreased in KOA [7,8]. As we have known, miR-199a-3p is documented to participate in cell apoptosis in osteosarcoma with its reduced expression [9]. In addition, hsa-miR-199a-3p is reduced in stimulated human OA chondrocytes [10]. ...
Aim
Studies have pivoted on the position of microRNAs (miRNAs) in knee osteoarthritis (KOA) but not the more specific function of miR-199-3p. Thus, this study is to uncover the mechanism of miR-199-3p in KOA.
Methods
Rats KOA models were established by modified Hulth method. miR-199-3p expression was observed in cartilage of KOA rats. The binding sites of miR-199-3p were predicted by bioinformatics analysis and the potential interaction between DNA methyltransferase 3A (DNMT3A) and miR-199-3p was verified by dual-luciferase reporter gene assay. Rats were injected with miR-199-3p agomir or antagomir and DNMT3A siRNA into the knee joint. Inflammatory response factors in serum and cartilage tissues, cell apoptosis, and pathological status of cartilage tissues were detected. Chondrocytes were isolated from KOA cartilages and treated with miR-199-3p mimic or inhibitor and DNMT3A siRNA. Chondrocyte proliferation and apoptosis were detected.
Results
miR-199-3p expression was suppressed in cartilage of KOA rats. Dual-luciferase reporter gene assay proved that a miR-199-3p-binding site was located in the 3′UTR of DNMT3A mRNA. Inflammation, chondrocyte apoptosis and cartilage pathological changes were improved by miR-199-3p agomir but aggravated by miR-199-3p antagomir. The effects of miR-199-3p antagomir on KOA rats were partially reversed by DNMT3A siRNA. miR-199-3p mimic or DNMT3A siRNA decreased KOA chondrocytes apoptosis and promoted proliferation. miR-199-3p inhibitor showed the opposite functions to miR-199-3p mimic. The effects of miR-199-3p inhibitor on chondrocytes were reversed by DNMT3A siRNA.
Conclusion
This study highlights that miR-199-3p up-regulation or down-regulation of DNMT3A induces chondrocyte proliferation and inhibits apoptosis in KOA, which may widen our eyes to treat patients with KOA.
... Expression of miR-34a downregulates Notch1 and causes cell cycle arrest and apoptosis [79]. C-Met, an oncogene involved in the cell cycle, and mTOR, a protein that controls cell cycle arrest and the response of the cells to stress and damage, are regulated by miR-34a [39,80,81]. MDM4, a p53-regulating protein, is another target of miR-34a. ...
Osteosarcoma (OS) is a primary bone malignancy, which has high incidence in children and adolescents. The affected cells and tissues show the properties of drug-resistance and the prognosis remains poor in OS, therefore there is an essential need for novel therapeutic approaches. MicroRNAs (miRNAs) expression pattern has been established to be involved in the pathogenesis of OS. miRNAs are small non-coding RNA molecules, which negatively regulate gene expression at post-transcriptional level. There are copious miRNAs that have a critical role in the onset of the disease, modulation of disease progression, and response to treatment. At the moment, the recently launched version 3.0 of Human MicroRNA Disease Database (HMDD v3.0) reports that 194 miRNAs are dysregulated in OS that might be involved in proliferation, migration, invasion, and epithelial-mesenchymal transition of tumor cells. The balance between oncogene and tumor suppressor miRNAs has vital importance in the final fate of the cell behaviors in OS. Additionally, networks of miRNAs may act in concert to induce oncogenic or tumor-suppressing properties during the initiation or progression of OS. Up or downregulation of these miRNAs affect the status of the disease, during or after therapy. To date, over 40 miRNAs have been identified in OS disease that possess oncogenic or tumor-suppressing properties, and treatment approaches are trying to establish a proper level of such miRNAs in favor of OS therapy. The role of miRNAs involved in the pathogenesis of OS and their therapeutic potential are the reference points in this review article.
... The p53-dependent miR-34c decreased runt-related transcription factor 2 (RUNX2) in OS, and Nutlin-3-mediated stabilization of p53 was found to be capable of promoting miR-34c level and reducing RUNX2, resulting in inhibition of U2OS cell proliferation [119]. MiR-34a and miR-199a-3p have been demonstrated to have important roles in blocking cell growth and elevating cell apoptosis via p53 signaling pathway by down-regulating its targets (mTOR, MET and MDM4 [an inhibitory factor of TP53] in OS [120]. An investigation reported that p53-associated miR-34a and miR-192 expression levels can be served as a prognostic marker for risk stratification in OS [121]. ...
Abstract MicroRNAs (miRNAs) involved in key signaling pathways and aggressive phenotypes of osteosarcoma (OS) was discussed, including PI3K/AKT/MTOR, MTOR AND RAF-1 signaling, tumor suppressor P53- linked miRNAs, NOTCH- related miRNAs, miRNA -15/16 cluster, apoptosis related miRNAs, invasion-metastasis-related miRNAs, and 14Q32-associated miRNAs cluster. Herrin, we discussed insights into the targeted therapies including miRNAs (i.e., tumor-suppressive miRNAs and oncomiRNAs). Using bioinformatics tools, the interaction network of all OS-associated miRNAs and their targets was also depicted.
... Up-regulation miR-9 [60,63,65,[75][76][77][78][79][80][81][82] miR-10a [60,64,65,75,83] miR-16 [52, 61-64, 75, 84] miR-17 [75,[84][85][86][87] miR-20a [60,66,86,[88][89][90][91][92][93] miR-20b [65,72,75,79,84,89,94,95] miR-21 [52, 61, 70, 71, 75, 76, 78, 84-87, 90, 96-114] miR-27a [53,62,64,85,115,116] miR-31 [62,71,76,85,89,96,98,[117][118][119][120] miR-92a [62,66,75,118,[121][122][123][124][125] miR-93 [75,84,89,118,126,127] miR-106a [64,75,84,118,128,129] miR-146a [52,75,90,103,130,131] miR-155 [52,53,75,78,79,84,117,118,[132][133][134] miR-196a [60,64,[135][136][137][138][139] miR-199b [63,79,85,140,141] miR-200a [61,75,89,105,117,126,142] miR-205 [52,64,85,117,138,[143][144][145] miR-210 [66,82,85,89,146] Down-regulation miR-29a [52,62,64,84,90,118,147,148] miR-34a [53,73,79,86,90,114,132,[149][150][151][152][153][154] miR-99a [61,64,73,75,89,110,118] miR-100 [52,62,89,75,84,86,118,155,156] miR-125b [52,61,78,75,84,117,118,151,157] miR-126 [52,86,117,[158][159][160] miR-143 [52,64,69,70,85,89,99,117,148,[161][162][163][164] miR-145 [52,64,69,77,84,85,89,118,139,[165][166][167][168][169] miR-149 [61,63,75,84,85,170] miR-193b [61,65,75,79,96] miR-195 [52,75,76,78,84,89,110,118,[171][172][173][174][175] miR-203 [53, 61, 63-65, 75, 79, 85, 86, 90, 176] miR-214 [89,98,126,[177][178][179][180][181][182][183] miR-218 [69,71,73,75,76,89,110,118,147,150,[184][185][186][187][188][189][190][191] miR-375 [75,84,118,150,192,193] miR-424 [52,78,117,118,150,[194][195][196][197][198] miR-497 [69,75,76,84,89,199,200] Fig. (1). Interaction between cervical epithelium, HPV infection, and the most significant miRNAs dysregulated in the cervical cancer progression (modified from Pardini et al. [14]). ...
... Up-regulation miR-9 [60,63,65,[75][76][77][78][79][80][81][82] miR-10a [60,64,65,75,83] miR-16 [52, 61-64, 75, 84] miR-17 [75,[84][85][86][87] miR-20a [60,66,86,[88][89][90][91][92][93] miR-20b [65,72,75,79,84,89,94,95] miR-21 [52, 61, 70, 71, 75, 76, 78, 84-87, 90, 96-114] miR-27a [53,62,64,85,115,116] miR-31 [62,71,76,85,89,96,98,[117][118][119][120] miR-92a [62,66,75,118,[121][122][123][124][125] miR-93 [75,84,89,118,126,127] miR-106a [64,75,84,118,128,129] miR-146a [52,75,90,103,130,131] miR-155 [52,53,75,78,79,84,117,118,[132][133][134] miR-196a [60,64,[135][136][137][138][139] miR-199b [63,79,85,140,141] miR-200a [61,75,89,105,117,126,142] miR-205 [52,64,85,117,138,[143][144][145] miR-210 [66,82,85,89,146] Down-regulation miR-29a [52,62,64,84,90,118,147,148] miR-34a [53,73,79,86,90,114,132,[149][150][151][152][153][154] miR-99a [61,64,73,75,89,110,118] miR-100 [52,62,89,75,84,86,118,155,156] miR-125b [52,61,78,75,84,117,118,151,157] miR-126 [52,86,117,[158][159][160] miR-143 [52,64,69,70,85,89,99,117,148,[161][162][163][164] miR-145 [52,64,69,77,84,85,89,118,139,[165][166][167][168][169] miR-149 [61,63,75,84,85,170] miR-193b [61,65,75,79,96] miR-195 [52,75,76,78,84,89,110,118,[171][172][173][174][175] miR-203 [53, 61, 63-65, 75, 79, 85, 86, 90, 176] miR-214 [89,98,126,[177][178][179][180][181][182][183] miR-218 [69,71,73,75,76,89,110,118,147,150,[184][185][186][187][188][189][190][191] miR-375 [75,84,118,150,192,193] miR-424 [52,78,117,118,150,[194][195][196][197][198] miR-497 [69,75,76,84,89,199,200] Fig. (1). Interaction between cervical epithelium, HPV infection, and the most significant miRNAs dysregulated in the cervical cancer progression (modified from Pardini et al. [14]). ...
... Up-regulation miR-9 [60,63,65,[75][76][77][78][79][80][81][82] miR-10a [60,64,65,75,83] miR-16 [52, 61-64, 75, 84] miR-17 [75,[84][85][86][87] miR-20a [60,66,86,[88][89][90][91][92][93] miR-20b [65,72,75,79,84,89,94,95] miR-21 [52, 61, 70, 71, 75, 76, 78, 84-87, 90, 96-114] miR-27a [53,62,64,85,115,116] miR-31 [62,71,76,85,89,96,98,[117][118][119][120] miR-92a [62,66,75,118,[121][122][123][124][125] miR-93 [75,84,89,118,126,127] miR-106a [64,75,84,118,128,129] miR-146a [52,75,90,103,130,131] miR-155 [52,53,75,78,79,84,117,118,[132][133][134] miR-196a [60,64,[135][136][137][138][139] miR-199b [63,79,85,140,141] miR-200a [61,75,89,105,117,126,142] miR-205 [52,64,85,117,138,[143][144][145] miR-210 [66,82,85,89,146] Down-regulation miR-29a [52,62,64,84,90,118,147,148] miR-34a [53,73,79,86,90,114,132,[149][150][151][152][153][154] miR-99a [61,64,73,75,89,110,118] miR-100 [52,62,89,75,84,86,118,155,156] miR-125b [52,61,78,75,84,117,118,151,157] miR-126 [52,86,117,[158][159][160] miR-143 [52,64,69,70,85,89,99,117,148,[161][162][163][164] miR-145 [52,64,69,77,84,85,89,118,139,[165][166][167][168][169] miR-149 [61,63,75,84,85,170] miR-193b [61,65,75,79,96] miR-195 [52,75,76,78,84,89,110,118,[171][172][173][174][175] miR-203 [53, 61, 63-65, 75, 79, 85, 86, 90, 176] miR-214 [89,98,126,[177][178][179][180][181][182][183] miR-218 [69,71,73,75,76,89,110,118,147,150,[184][185][186][187][188][189][190][191] miR-375 [75,84,118,150,192,193] miR-424 [52,78,117,118,150,[194][195][196][197][198] miR-497 [69,75,76,84,89,199,200] Fig. (1). Interaction between cervical epithelium, HPV infection, and the most significant miRNAs dysregulated in the cervical cancer progression (modified from Pardini et al. [14]). ...
Human papillomavirus (HPV) is among the most common sexually transmitted infections
in both females and males across the world that generally do not cause symptoms and are characterized
by high rates of clearance. Persistent infections due at least to twelve well-recognized high-risk
(HR) or oncogenic genotypes, although less frequent, can occur, leading to diseases and malignancies,
principally cervical cancer. Three vaccination strategies are currently available for preventing
certain HR HPVs-associated diseases, infections due to HPV6 and HPV11 low-risk types, as well as
for providing cross-protection against non-vaccine genotypes. Nevertheless, the limited vaccine coverage
hampers reducing the burden of HPV-related diseases globally.
For HR HPV types, especially HPV16 and HPV18, the E6 and E7 oncoproteins are needed for cancer
development. As for other tumors, even in cervical cancer, non-coding microRNAs (miRNAs)
are involved in post-transcriptional regulation, resulting in aberrant expression profiles.
In this study, we provide a summary of the epidemiological background for HPV occurrence and
available immunization programs. In addition, we present an overview of the most relevant evidence
of miRNAs deregulation in cervical cancer, underlining that targeting these biomolecules could lead
to wide translational perspectives, allowing better diagnosis, prognosis and therapeutics, and with
valuable applications in the field of prevention. The literature on this topic is rapidly growing, but
advanced investigations are required to achieve more consistent findings on the up-regulated and
down-regulated miRNAs in cervical carcinogenesis. Because the expression of miRNAs is heterogeneously
reported, it may be valuable to assess factors and risks related to individual susceptibility.
... Although several miRNAs have been found to be deregulated in osteosarcoma cells and tissues, the exact mechanism by how miRNA regulated the tumorigenesis is still not fully elucidated [31][32][33][34]. Our study showed that miR-423-5p expression was decreased in osteosarcoma tissues and cell lines. ...
Background/Aims: Increasing evidences suggest that dysregulated expression of miRNAs contributes to the progression of various tumors. However, the underlying function of miR-423-5p in osteosarcoma remains unexplored. Methods: The expression of miR-423-5p and STMN1 were determined in osteosarcoma samples and cell lines via quantitative real-time PCR. Colony formation and Cell Counting Kit-8 (CCK-8) assays were performed to measure cell proliferation ability and transwell analysis was used to detect cell invasion, and dual luciferase reporter assay was perform to analysis the interaction between the miR-423-5p and STMN1. Results: The expression levels of miR-423-5p and STMN1 in the osteosarcoma tissues and cell lines were measured by qRT-PCR. Cell viability was determined using the clone formation and CCK-8 assays. A dual-luciferase reporter and Western blot were performed to stdudy the target gene of miR-423-5p. Here, we showed that miR-423-5p expression was downregulated in osteosarcoma tissues and cell lines. However, the expression of stathmin1 (STMN1) was downregulated in osteosarcoma tissues and cell lines. Moreover, STMN1 expression level was negatively correlated with the miR-423-5p expression in the osteosarcoma tissues. We identified STMN1 was a direct target gene of miR-423-5p in osteosarcoma cell. Overexpression of miR-423-5p inhibited osteosarcoma cell proliferation, colony formation and invasion. Furthermore, we demonstrated that STMN1 was involved in miR-423-5p-mediated cell behavior such as cell proliferation, colony formation and invasion in the osteosarcoma cell. Conclusion: Our present study indicated that miR-423-5p acted as a tumor suppressor gene in osteosarcoma partly through inhibiting STMN1 expression.
... Besides, it has been discovered that miR-195-5p involved in the inhibition of osteosarcoma cell migration and invasion by targeting fatty acid synthase (FASN) [78], while miR-199a-3p regulated the p53 signaling pathway and inhibits osteosarcoma cell growth, migration, and induce apoptosis [79,80]. ...
... A current study showed that MVIH might control HCC cell vitality by sponging and repressing the expression of miR-199a (Shi et al., 2015). Several reports have shown that miR-199a acts as a tumor repressor, promotes tumor cell apoptosis, and inhibits cell proliferation and migration in several cancers (Tian et al., 2014;Wang et al., 2014b;Kinose et al., 2015). Yuan et al. (2012b) found that MVIH could activate tumor-inducing angiogenesis by diminishing the secretion of phosphoglycerate kinase 1 (PGK1), which is a glycolytic enzyme that catalyzes the conversion of 1.3-diphosphoglycerate to 3-phosphoglycerate. ...
Eukaryotic lncRNAs are RNA molecules defined to be greater than 200 bp in length that are not translated to a protein and operate through several mechanisms, including participating in chromatin remodeling and methylation, influencing the integrity and stability of proteins and complexes, or acting as a sponge for miRNA inhibition. A number of recent studies have concentrated on the relationship between long non-coding RNAs (lncRNAs) and cancer. Hepatocellular carcinoma (HCC) is the most prevalent histological type of liver tumors, accounting for about 80 % of the cases worldwide. Lack of proper molecular markers for diagnosis of HCC and treatment evaluation is a significant problem. Dysregulated expression of HCC-related lncRNAs such as MEG-3, MALAT1, HULC, HOTAIR, and H19 have been identified and closely related with tumorigenesis, metastasis, prognosis and diagnosis. In this review, we summarized recent highlighted functions and molecular mechanisms of the most extensively studied lncRNAs in the pathophysiology of hepatocellular carcinoma and their potential for serving as probable therapeutic targets. © 2018, Leibniz Research Centre for Working Environment and Human Factors. All rights reserved.
