scholarly journals MicroRNA Involvement in Osteosarcoma

Sarcoma ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Eisuke Kobayashi ◽  
Francis J. Hornicek ◽  
Zhenfeng Duan

Osteosarcoma (OS) is the most common primary malignant bone tumor, usually arising in the long bones of adolescents and young adults. While our knowledge of the molecular pathogenesis of OS has increased in recent years, we are still far from a comprehensive understanding of the molecular mechanisms of the disease, such as its tumorigenesis, specific mediators of disease progression, occurrence of chemoresistance, and development of metastasis. After the recent discovery of microRNAs (miRNAs), their critical roles in molecular biological processes have been of great interest in the cancer research field, including research on sarcomas. MiRNAs are highly conserved noncoding RNAs which play important roles as oncogenic or suppressive genes to simultaneously regulate multiple targets. Recent genome-wide screening using miRNA expression profiles has identified specific miRNA expression patterns that are associated with the biological and clinical properties of cancers. Additionally, miRNAs and their target genes or proteins can be potential novel biomarkers or therapeutic targets for cancer. However, there are several challenges that must be addressed in order to translate miRNA-based therapeutics to the clinical setting. In this review, we summarize the current understanding of the roles that miRNAs play in OS, and highlight their potential as biomarkers or therapeutic targets.

BMC Genomics ◽  
2022 ◽  
Vol 23 (1) ◽  
Author(s):  
Haitao Xing ◽  
Yuan Li ◽  
Yun Ren ◽  
Ying Zhao ◽  
Xiaoli Wu ◽  
...  

Abstract Background MicroRNAs (miRNAs) are endogenous, non-coding small functional RNAs that govern the post-transcriptional regulatory system of gene expression and control the growth and development of plants. Ginger is an herb that is well-known for its flavor and medicinal properties. The genes involved in ginger rhizome development and secondary metabolism have been discovered, but the genome-wide identification of miRNAs and their overall expression profiles and targets during ginger rhizome development are largely unknown. In this study, we used BGISEQ-500 technology to perform genome-wide identification of miRNAs from the leaf, stem, root, flower, and rhizome of ginger during three development stages. Results In total, 104 novel miRNAs and 160 conserved miRNAs in 28 miRNA families were identified. A total of 181 putative target genes for novel miRNAs and 2772 putative target genes for conserved miRNAs were predicted. Transcriptional factors were the most abundant target genes of miRNAs, and 17, 9, 8, 4, 13, 8, 3 conserved miRNAs and 5, 7, 4, 5, 5, 15, 9 novel miRNAs showed significant tissue-specific expression patterns in leaf, stem, root, flower, and rhizome. Additionally, 53 miRNAs were regarded as rhizome development-associated miRNAs, which mostly participate in metabolism, signal transduction, transport, and catabolism, suggesting that these miRNAs and their target genes play important roles in the rhizome development of ginger. Twelve candidate miRNA target genes were selected, and then, their credibility was confirmed using qRT-PCR. As the result of qRT-PCR analysis, the expression of 12 candidate target genes showed an opposite pattern after comparison with their miRNAs. The rhizome development system of ginger was observed to be governed by miR156, miR319, miR171a_2, miR164, and miR529, which modulated the expression of the SPL, MYB, GRF, SCL, and NAC genes, respectively. Conclusion This is a deep genome-wide investigation of miRNA and identification of miRNAs involved in rhizome development in ginger. We identified 52 rhizome-related miRNAs and 392 target genes, and this provides an important basis for understanding the molecular mechanisms of the miRNA target genes that mediate rhizome development in ginger.


2018 ◽  
Author(s):  
Fang Wang ◽  
Qian-wen Yang ◽  
Wen-Jie Zhao ◽  
Qi-Yan Du ◽  
Zhong-Jie Chang

ABSTRACTMicroRNAs (miRNAs) are endogenous small non-coding RNAs that negatively regulate gene expression by targeting specific mRNAs; they are involved in the modulation of important mRNA networks involved in toxicity. Atrazine is a known endocrine-disrupting chemical, whose molecular mechanisms are unknown. In this study, common carp (Cyprinus carpio) gonads at two key developmental stages were exposed to 0.428 ppb atrazine for 24 h in vitro. MiRNA expression profiles were analysed to identify miRNAs related to gonad development and to reveal the atrazine mechanisms interfering with gonad differentiation. Atrazine exposure caused significant alteration of multiple miRNAs. Compared with the juvenile ovary, more miRNAs were down-regulated in juvenile testis, some of these down-regulated miRNAs target the steroid hormone biosynthesis pathway related-genes. Predicted target genes of differently-expressed miRNAs after exposure to atrazine were involved in many reproductive biology signalling pathways. We suggest that these target genes may have important roles in atrazine-induced reproductive toxicity by altering miRNAs expression. Our results also indicate that atrazine can up-regulate aromatase expression through miRNAs, which supports the hypothesis that atrazine has endocrine-disrupting activity by altering the expression of genes of the Hypothalamus-Pituitary-Gonad axis through its corresponding miRNAs. This study tells us the following conclusions: 1. Atrazine exposure results in significant alterations of miRNAs whose predicted target genes are associated with reproductive processes. 2. In the primordial gonad, atrazine promoted the expression of early gonad-determining genes by decreasing specific miRNAs. 3. In the juvenile gonad, atrazine promoted the biosynthesis of steroid hormones.


2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Jufeng Zhang ◽  
Xia Luo ◽  
Huiming Li ◽  
Ling Deng ◽  
Ying Wang

Colorectal cancer (CRC) is one of the most common malignancies resulting in high mortality worldwide. Signal transducer and activator of transcription 3 (STAT3) is an oncogenic transcription factor which is frequently activated and aberrantly expressed in CRC. MicroRNAs (miRNAs) are a class of small noncoding RNAs which play important roles in many cancers. However, little is known about the global miRNA profiles mediated by STAT3 in CRC cells. In the present study, we applied RNA interference to inhibit STAT3 expression and profiled the miRNA expression levels regulated by STAT3 in CRC cell lines with deep sequencing. We found that 26 and 21 known miRNAs were significantly overexpressed and downexpressed, respectively, in the STAT3-knockdown CRC cell line SW480 (SW480/STAT3-siRNA) compared to SW480 transfected with scrambled siRNAs (SW480/siRNA-control). The miRNA expression profiling was then validated by quantitative real-time PCR for selected known miRNAs. We further predicted the putative target genes for the dysregulated miRNAs and carried out functional annotation including GO enrichment and KEGG pathway analysis for selected miRNA targets. This study directly depicts STAT3-mediated miRNA profiles in CRC cells, which provides a possible way to discover biomarkers for CRC therapy.


2020 ◽  
Vol 21 (7) ◽  
pp. 722-734
Author(s):  
Adele Soltani ◽  
Arefeh Jafarian ◽  
Abdolamir Allameh

micro (mi)-RNAs are vital regulators of multiple processes including insulin signaling pathways and glucose metabolism. Pancreatic β-cells function is dependent on some miRNAs and their target mRNA, which together form a complex regulative network. Several miRNAs are known to be directly involved in β-cells functions such as insulin expression and secretion. These small RNAs may also play significant roles in the fate of β-cells such as proliferation, differentiation, survival and apoptosis. Among the miRNAs, miR-7, miR-9, miR-375, miR-130 and miR-124 are of particular interest due to being highly expressed in these cells. Under diabetic conditions, although no specific miRNA profile has been noticed, the expression of some miRNAs and their target mRNAs are altered by posttranscriptional mechanisms, exerting diverse signs in the pathobiology of various diabetic complications. The aim of this review article is to discuss miRNAs involved in the process of stem cells differentiation into β-cells, resulting in enhanced β-cell functions with respect to diabetic disorders. This paper will also look into the impact of miRNA expression patterns on in vitro proliferation and differentiation of β-cells. The efficacy of the computational genomics and biochemical analysis to link the changes in miRNA expression profiles of stem cell-derived β-cells to therapeutically relevant outputs will be discussed as well.


Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1388-1388
Author(s):  
Xiaomei Chen ◽  
Fang Liu ◽  
Wei Xiong ◽  
Xiangjun Chen ◽  
Cong Lu ◽  
...  

Abstract Abstract 1388 Microvesicles(MVs) are small exosomes of endocytic origin released by normal healthy or damaged cell types, including leukemic cells. MVs have been considered as cell dust, however, recent data bring evidences that MVs generated during cell activation or apoptosis can transfer biologic messages between different cell types. MicroRNAs (miRNAs) have been demonstrated to be aberrantly expressed in leukemia and the overall miRNA expression could differentiate normal versus leukemia. The MVs expressing miRNAs were found in the primary tumors. However it is currently unknown whether miRNA content changes in MVs derived from leukemic cells. Here we compared the miRNA expression in leukemia-derived MVs to corresponding leukemia cells and analysed their roles in leukemia. K562 cells were cultured and collected. MVs derived from K562 cells were also isolated. The presence and levels of specific miRNAs from both MVs derived from K562 cells and K562 cells were determined by Agilent miRNA microarray analysis probing for 888 miRNAs. Some selected miRNAs were verified by real time qRT-PCR. Bioinformatic software tools were used to predict the target genes of identified miRNAs and define their function. Our results showed that 77 and 122 miRNAs were only expressed in MVs and K562 cells, respectively. There were significant differences in miRNA expression profiles between MVs and K562 cells. We also found that 112 miRNAs were co-expressed in MVs and K562 cells. This observaton may suggest that compartmentalization of miRNAs from cells into to MVs, for at least some miRNAs, is an active (selective) process. Among those abnormally expressed miRNAs, some have been proposed oncomiRNAs or tumor suppressors. For example, miR-155, has been proposed as oncomiRNA, was abnormally expressed only in MVs in our study, suggesting that oncomiRNA was present in MVs. Further analysis revealed that 39 potential target genes regulated by miR-155. Among them, 4 genes involed in oncogenes and the signal genes. OncomiRNAs such as miR-27a and miR-21 expressed in both MVs and corresponding cells, indicating that MVs bear miRNA characteristic of the cell origin. MVs, released into the leukemia microenvironment, play an important role in leukemia. In contrast to oncomiRNAs, if miRNA is associated with tumor suppressive activity, it is regarded as a tumor suppressor (oncosuppressor). The aberrantly expressed miR-125a-3p, miR-125-5p,miR-27b, which have implicated as tumor suppressors, appear in both cellular and MVs of leukemia in our study. MiR-125a-3p, miR-125-5p and miR-27b regulated 308 potential target genes. To our knowledge, 10 of them are tumor suppression genes. It is possible that these aberrantly expressed tumor suppressor miRNAs decreased or lost their roles of tumor suppression, which led to decrease or loss their roles of regulating their target genes including oncogenes, consequently resulted in leukemia. Since K562 cells presented t(9;22), we further examined the predicted function of the 6 expressed miRNAs located in chrosome 9 (hsa-miR-188-5p,hsa-miR-602)and 22(hsa-let-7b,hsa-miR-1249,hsa-miR-130b,hsa-miR-185), which expressed both in the MVs and K562 cells. Using the TargetScan, we found 442 predicted targets regulated by 6 miRNAs. Those miRNAs may play roles in leukemia via these 422 genes. This study is the first to identify and define miRNA expression between K562 cells presented t(9;22), derived from K562 cells and their corresponding cells. We found significant differences in miRNA expression between MVs and corresponding leukemia. K562 cells released MVs riched in miRNAs including oncomiRNAs or tumor suppressor miRNAs into leukemia microenvironment, which play a role in leukemia via regulating their targer genes including oncogenes, consequently resulted in leukemia. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1488-1488
Author(s):  
Xiaomei Chen ◽  
Wei Xiong ◽  
Xiangjun Chen ◽  
Cong Lu ◽  
Fang Liu ◽  
...  

Abstract Abstract 1488 Microvesicles (MVs) released by leukemia cells constitute an important part of the leukemia microenvironment. As a cell-to-cell communication tool, MVs transfer microRNA(miRNA) between cells. MVs miRNAs may be valuable not only as a diagnostic tool but may also provide an insight in the role of miRNAs playing in the underlying of pathophysiologic processes of various leukemia. It is worth evaluating whether MVs possess some unique miRNA content depending on their corresponding leukemia origin that could be applicable in diagnosis. Hence, we determined the miRNA expression profiles of ALL-derived MVs using Agilent miRNA microarray analysis. The five miRNAs obtained by microarray profiling were validated using real-time PCR. The putative target genes were predicted by bioformation software. Here, we provided MVs miRNA patterns derived from the healthy controls, B-ALL cell line Nalm 6 cells and T-ALL cell line Jurkat cells. We identified 182 dysregulated miRNAs in MVs derived from Nalm 6 cells as compared with MVs from normal controls (P<0.05); both up regulated(123/182) and down regulated(59/182) expressions were observed. Likewise 166 miRNAs were significantly differentially expressed in MVs derived from Jurkat cells versus MVs from normal peripheral blood (P<0.05), 114 miRNAs of which (114/166) were up expression and 52 miRNAs (52/166) were down expression. We also fould that 44 miRNAs were only detected in B-ALL-derived MVs. MiR-1290, miR-1246, miR-1268, miR-1226, and miR-424 were top 5 expressed in Nalm 6 derived MVs, suggesting that those miRNAs may play an important role in B-ALL. We observed that 16 miRNAs detected only in T cell derived MVs. MiR-96 is up regulated in MVs from T-ALL cells but not expressed in B-ALL. Specific and functional target sites for miR-96, exist in the 3'-UTR of the miRNA that encodes the putative tumor suppressor transcription factor FOXO1. The expression signatures of miR-96 could discriminate B-ALL from T-ALL. In contrast, the MVs from B-ALL cell line, shared 100 miRNAs with MVs from T-ALL cell line, suggestting that those miRNAs play roles in both B-and T-ALL. Of 100 miRNAs, 99 miRNAs were high expression, indicating that miRNAs were active in ALL. This obsearvation suggusted that miRNA differential expression in MVs were partially significantly related to subtypes of acute lymphoblastic leukemia. Intriguing is that miR1290 is top higher expression both in MVs derived from Nalm6 cells and from Jurkat cells; miR-1290 is 475-fold higher expressed in Nalm 6 derived MVs versus MVs from normal cells, whereas this miRNA is 245-fold higher expressed in Jurkat cells. Five of these miRNAs were selected to be further assayed and validated by PCR. The qRT-PCR results correlated well with the microarray data. In addition, we found seven miRNAs(miR-148b, miR-484, miR-let-7f, let-7a, miR-223, miR16 and miR-27b) were located near the 11q23 chromosomal region. With bioinformatic tools (TargetScan), we predicted potential target genes for those miRNAs that exhibited altered expression in MVs from B-ALL and T-ALL. The p85 subunit of phosphatidylinositol 3-kinase (PI3-K) was found to be a potential target of miR-320. Of particular interest, we found that protein tyrosine phosphatase-like member b (PTPLB) may be a potential target of miR-1290. The 474-fold increase in miR-1290 in MVs from Nalm 6 cells, indicating that miR-1290 may participate in the modulation of leukemia by targeting PTPLB, a specific, negative regulator of p210 bcr-abl signal. In conclusion, we identified miRNAs and found that miRNA expression profiles were ALL subtype-specific. Altered miRNA expression levels may lead to an inappropriate expression of target oncoproteins or target tumor suppressors, thereby facilitating the development of leukemia. These findings expanded the potential diagnostic markers of leukemia and provided useful information to ALL pathogenesis. Disclosures: No relevant conflicts of interest to declare.


2016 ◽  
Vol 17 (5) ◽  
pp. 656 ◽  
Author(s):  
Antonina Parafioriti ◽  
Caterina Bason ◽  
Elisabetta Armiraglio ◽  
Lucia Calciano ◽  
Primo Daolio ◽  
...  

2014 ◽  
Vol 170 (4) ◽  
pp. 583-591 ◽  
Author(s):  
David Velázquez-Fernández ◽  
Stefano Caramuta ◽  
Deniz M Özata ◽  
Ming Lu ◽  
Anders Höög ◽  
...  

BackgroundThe adrenocortical adenoma (ACA) entity includes aldosterone-producing adenoma (APA), cortisol-producing adenoma (CPA), and non-hyperfunctioning adenoma (NHFA) phenotypes. While gene mutations and mRNA expression profiles have been partly characterized, less is known about the alterations involving microRNA (miRNA) expression.AimTo characterize miRNA expression profile in relation to the subtypes of ACAs.Subjects and methodsmiRNA expression profiles were determined in 26 ACAs (nine APAs, ten CPAs, and seven NHFAs) and four adrenal references using microarray-based screening. Significance analysis of microarrays (SAM) was carried out to identify differentially expressed miRNAs between ACA and adrenal cortices or between tumor subtypes. Selected differentially expressed miRNAs were validated in an extended series of 43 ACAs and ten adrenal references by quantitative RT-PCR.ResultsAn hierarchical clustering revealed separate clusters for APAs and CPAs, while the NHFAs were found spread out within the APA/CPA clusters. When NHFA was excluded, the clustering analysis showed a better separation between APA and CPA. SAM analysis identified 40 over-expressed and three under-expressed miRNAs in the adenomas as compared with adrenal references. Fourteen miRNAs were common among the three ACA subtypes. Furthermore, we found specific miRNAs associated with different tumor phenotypes.ConclusionThe results suggest that miRNA expression profiles can distinguish different subtypes of ACA, which may contribute to a deeper understanding of ACA development and potential therapeutics.


2021 ◽  
Vol 12 ◽  
Author(s):  
Simone Howard ◽  
Shakyra Richardson ◽  
Ifeyinwa Benyeogor ◽  
Yusuf Omosun ◽  
Kamran Dye ◽  
...  

Vaccine-induced immune responses following immunization with promising Chlamydia vaccines protected experimental animals from Chlamydia-induced upper genital tract pathologies and infertility. In contrast, primary genital infection with live Chlamydia does not protect against these pathologies. We hypothesized that differential miRNA profiles induced in the upper genital tracts (UGT) of mice correlate with the disparate immunity vs. pathologic outcomes associated with vaccine immunization and chlamydial infection. Thus, miRNA expression profiles in the UGT of mice after Chlamydia infection (Live EB) and immunization with dendritic cell (DC)-based vaccine (DC vaccine) or VCG-based vaccine (VCG vaccine) were compared using the NanoString nCounter Mouse miRNA assay. Of the 602 miRNAs differentially expressed (DE) in the UGT of immunized and infected mice, we selected 58 with counts &gt;100 and p-values &lt; 0.05 for further analysis. Interestingly, vaccine immunization and Chlamydia infection induced the expression of distinct miRNA profiles with a higher proportion in vaccine-immunized compared to Chlamydia infected mice; DC vaccine (41), VCG vaccine (23), and Live EB (15). Hierarchical clustering analysis showed notable differences in the uniquely DE miRNAs for each experimental group, with DC vaccine showing the highest number (21 up-regulated, five down-regulated), VCG vaccine (two up-regulated, five down-regulated), and live EB (two up-regulated, four down-regulated). The DC vaccine-immunized group showed the highest number (21 up-regulated and five down-regulated compared to two up-regulated and four down-regulated in the live Chlamydia infected group). Pathway analysis showed that the DE miRNAs target genes that regulate several biological processes and functions associated with immune response and inflammation. These results suggest that the induction of differential miRNA expression plays a significant role in the disparate immunity outcomes associated with Chlamydia infection and vaccination.


2022 ◽  
Vol 12 ◽  
Author(s):  
Xiaodong Zhao ◽  
Zhibin Ji ◽  
Rong Xuan ◽  
Aili Wang ◽  
Qing Li ◽  
...  

The liver is the largest digestive gland in goats with an important role in early metabolic function development. MicroRNAs (miRNA) are crucial for regulating the development and metabolism in the goat liver. In the study, we sequenced the miRNAs in the liver tissues of the goat kid to further research their regulation roles in early liver development. The liver tissues were procured at 5-time points from the Laiwu black goats of 1 day (D1), 2 weeks (W2), 4 weeks (W4), 8 weeks (W8), and 12 weeks (W12) after birth, respectively with five goats per time point, for a total of 25 goats. Our study identified 214 differential expression miRNAs, and the expression patterns of 15 randomly selected miRNAs were examined among all five age groups. The Gene ontology annotation results showed that differential expression miRNA (DE miRNA) target genes were significantly enriched in the fatty acid synthase activity, toxin metabolic process, cell surface, and antibiotic metabolic process. The KEGG analysis result was significantly enriched in steroid hormone synthesis and retinol metabolism pathways. Further miRNA-mRNA regulation network analysis reveals 9 differently expressed miRNA with important regulation roles. Overall, the DE miRNAs were mainly involved in liver development, lipid metabolism, toxin related metabolism-related biological process, and pathways. Our results provide new information about the molecular mechanisms and pathways in the goat kid liver development.


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