MicroRNA array of SH-SY5Y cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: 
Yolanda Espinosa-Parrilla Alicia Gallego
PROVIDER: E-MTAB-3617 | ArrayExpress | 2016-04-03
REPOSITORIES: ArrayExpress
Publications
Functional Implications of Human-Specific Changes in Great Ape microRNAs.
Gallego Alicia A Melé Marta M Balcells Ingrid I García-Ramallo Eva E Torruella-Loran Ignasi I Fernández-Bellon Hugo H Abelló Teresa T Kondova Ivanela I Bontrop Ronald R Hvilsom Christina C Navarro Arcadi A Marquès-Bonet Tomàs T Espinosa-Parrilla Yolanda Y
PloS one 20160422 4
microRNAs are crucial post-transcriptional regulators of gene expression involved in a wide range of biological processes. Although microRNAs are highly conserved among species, the functional implications of existing lineage-specific changes and their role in determining differences between humans and other great apes have not been specifically addressed. We analyzed the recent evolutionary history of 1,595 human microRNAs by looking at their intra- and inter-species variation in great apes usi ...[more]
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Project description:microRNAs are crucial post-transcriptional regulators of gene expression involved in a wide range of biological processes. Although microRNAs are highly conserved among species, the functional implications of existing lineage-specific changes and their role in determining differences between humans and other great apes have not been specifically addressed. We analyzed the recent evolutionary history of 1,595 human microRNAs by looking at their intra- and inter-species variation in great apes using high-coverage sequenced genomes of 82 individuals including gorillas, orangutans, bonobos, chimpanzees and humans. We explored the strength of purifying selection among microRNA regions and found that the seed and mature regions are under similar and stronger constraint than the precursor region. We further constructed a comprehensive catalogue of microRNA species-specific nucleotide substitutions among great apes and, for the first time, investigated the biological relevance that human-specific changes in microRNAs may have had in great ape evolution. Expression and functional analyses of four microRNAs (miR-299-3p, miR-503-3p, miR-508-3p and miR-541-3p) revealed that lineage-specific nucleotide substitutions and changes in the length of these microRNAs alter their expression as well as the repertoires of target genes and regulatory networks. We suggest that the studied molecular changes could have modified crucial microRNA functions shaping phenotypes that, ultimately, became human-specific. Our work provides a frame to study the impact that regulatory changes may have in the recent evolution of our species.
2016-01-01 | S-EPMC4841587 | BioStudies
Project description:BACKGROUND:MicroRNAs (miRNAs) play a role in regulating osteogenic differentiation (OD) of mesenchymal stem cells by inhibiting mRNAs translation under cyclic strain. miR-503-3p was downregulated in OD of human adipose-derived stem cells (hASCs) in vivo under cyclic strain in our previous study, while it might target the Wnt/?-catenin (W-?) pathway. In this study, we explored miR-503-3p's role in OD of hASCs under cyclic strain. METHODS:OD of hASCs was induced by cyclic strain. Bioinformatic and dual luciferase analyses were used to confirm the relationship between Wnt2/Wnt7b and miR-503-3p. Immunofluorescence was used to detect the effect of miR-503-3p on Wnt2/Wnt7b and ?-catenin in hASCs transfected with miR-503-3p mimic and inhibitor. Mimic, inhibitor, and small interfering RNA (siRNA) transfected in hASCs to against Wnt2 and Wnt7b. Quantitative real-time PCR (RT-PCR) and western blot were used to examine the OD and W-? pathway at the mRNA and protein levels, respectively. Immunofluorescence was performed to locate ?-catenin. ALP activity and calcium were detected by colorimetric assay. RESULTS:Results of immunophenotypes by flow cytometry and multi-lineage potential confirmed that the cultured cells were hASCs. Results of luciferase reporter assay indicated that miR-503-3p could regulate the expression levels of Wnt2 and Wnt7b by targeting their respective 3'-untranslated region (UTR). Under cyclic strain, gain- or loss-function of miR-503-3p studies by mimic and inhibitor revealed that decreasing expression of miR-503-3p could significantly bring about promotion of OD of hASCs, whereas increased expression of miR-503-3p inhibited OD. Furthermore, miR-503-3p high-expression reduced the activity of the W-? pathway, as indicated by lowering expression of Wnt2 and Wnt7b, inactive ?-catenin in miR-503-3p-treated hASCs. By contrast, miR-503-3p inhibition activated the W-? pathway. CONCLUSIONS:Collectively, our findings indicate that miR-503-3p is a negative factor in regulating W-? pathway by Wnt2 and Wnt7b, which inhibit the OD of hASCs under cyclic strain.
2020-01-01 | S-EPMC7382842 | BioStudies
Project description:Gastric cancer (GC) remains a leading cause of cancer?associated mortality globally. Emerging evidence suggests that microRNAs (miRs) function as oncogenes or tumor suppressors, contributing to various aspects of cancer progression, including invasion and metastasis. In the present study, the specific role of miR?299?3p in the invasion of GC cells was investigated. The expression level of miR?299?3p was measured using reverse transcription?quantitative PCR and in situ hybridization in human GC tissues. Effects of miR?299?3p on GC cell invasion were determined by Transwell assay. Bioinformatics and luciferase reporter assays were performed to identify and verify the downstream effectors of miR?299?3p. miR?299?3p expression analysis in clinical GC samples revealed a significant downregulation of miR?299?3p compared with non?tumor tissues. Inhibition of miR?299?3p promoted the invasive abilities of GC cells, whereas its overexpression significantly suppressed cell invasion. Bioinformatics and luciferase reporter assays identified heparanase (HPSE) as a direct target of miR?299?3p, the ectopic expression of which reversed the impairment in cell invasion induced by miR?299?3p upregulation. Furthermore, HPSE expression was negatively associated with miR?299?3p levels in human GC tissues. Overall, the present study indicated that miR?299?3p functions as a tumor suppressor by directly targeting HPSE, highlighting its potential as a target for the treatment of GC.
2019-01-01 | S-EPMC6691259 | BioStudies
Project description:Ovarian cancer is the most lethal gynecological tumor, and the 5?year survival rate is only ~40%. The poor survival rate is due to cancer diagnosis at an advanced stage, when the tumor has metastasized. A better understanding of the molecular pathogenesis of tumor growth and metastasis is needed to improve patient prognosis. MicroRNAs (miRs) regulate carcinogenesis and development of cancers. However, the role of miR?508?3p in ovarian cancer remains largely unknown. Thus, the present study aimed to investigate the possible functions of miR?508?3p in the modulation of development of ovarian cancer. The results of the present study demonstrated that miR?508?3p mimics inhibited ovarian cancer cell proliferation, migration and invasion. Reporter gene assay results demonstrated that miR?508?3p suppressed cancer cell proliferation by directly targeting the 3'?untranslated region (UTR) of cyclin A2 (CCNA2) and suppressed migration and invasion by directly targeting the 3'?UTR of matrix metalloproteinase 7 (MMP7). In addition, high CCNA2 and MMP7 expression levels were associated with low miR?508?3p expression in ovarian cancer tissues. Furthermore, miR?508?3p and CCNA2 were independent predictors for overall survival in patients with ovarian cancer. To the best of our knowledge, this is the first study to demonstrated that miR?508?3p suppressed ovarian cancer development by directly targeting CCNA2 and MMP7. The results of this study suggested the potential value of miR?508?3p and CCNA2 as prognostic indicators and therapeutics for ovarian cancer.
2020-01-01 | S-EPMC7252466 | BioStudies
Project description:Cancer stem cells (CSCs) with self-renewal abilities endorse cellular heterogeneity, resulting in metastasis and recurrence. However, there are no promising therapeutics directed against CSCs. Herein, we found that miR-503-3p inhibited tumor growth via the regulation of CSC proliferation and self-renewal. miR-503-3p, isolated from human adipose stem cell- (ASC-) derived exosomes, suppressed initiation and progression of CSCs as determined by anchorage-dependent (colony formation) and anchorage-independent (tumorsphere formation) assays. The expression of pluripotency genes was significantly decreased in miR-503-3p-treated CSCs. Furthermore, xenografts, which received miR-503-3p, exhibited remarkably reduced tumor growth in vivo. Thus, miR-503-3p may function as a stemness-attenuating factor via cell-to-cell communications.
2018-01-01 | S-EPMC5904772 | BioStudies
Project description:Introduction:Accumulating evidence has demonstrated that circular RNAs (circRNAs) play a key role in the tumorigenesis of various types of cancers, including clear cell renal cell carcinoma (ccRCC). Materials and Methods:Reverse transcription-quantitative polymerase chain reaction was used to detect the expression of circRNA homeodomain interacting protein kinase 3 (circHIPK3) and microRNAs (miRNAs), including miR-508-3p. The clinical measurement of circHIPK3 was evaluated by Kaplan-Meier survival analysis and receiver operating characteristic analysis. Cell Counting Kit-8 and Transwell chamber assays were performed to determine the changes in the proliferative and metastatic ability of A498 and 786-O cells. C-X-C motif chemokine ligand 13 (CXCL13) protein expression was detected by Western blot analysis. The targeted binding effect between miR-508-3p and circHIPK3 or CXCL13 was confirmed by constructed luciferase and RNA immunoprecipitation (RIP) assays, respectively. Fluorescence in situ hybridization (FISH) assay was used to measure the subcellular localization of circHIPK3 and miR-508-3p. Results:It was found that circHIPK3 was markedly upregulated in ccRCC tissue and cell lines, and circHIPK3-upregulation was closely correlated with poor clinicopathological features in patients with ccRCC. It was found that both miR-508-3p and circHIPK3 were localized in the cytoplasm of ccRCC cells. The up- and downregulation of circHIPK3 positively regulated ccRCC cell proliferation and metastasis, and this regulatory effect was reversed by miR-508-3p. Through luciferase and RIP assays, it was confirmed that circHIPK3 could interacted with miR-508-3p. Furthermore, it was revealed that CXCL13, which was negatively correlated with miR-508-3p, was upregulated in ccRCC. It was also shown that CXCL13 was a downstream target of miR-508-3p. miR-508-3p suppressed ccRCC cell proliferation and metastasis by targeting CXCL13. Lastly, it was demonstrated that circHIPK3 promoted CXCL13 to facilitate ccRCC cell proliferation and metastasis by decoying miR-508-3p. Conclusion:In brief, the results of the present study showed that circHIPK3 promoted ccRCC cell proliferation and metastasis by altering miR-5083p/CXCL13 signaling. The present findings might provide a novel target for the molecular treatment of ccRCC.
2020-01-01 | S-EPMC7422843 | BioStudies
Project description:Prostate cancer (PCa) is one of the most common cancers to affect men worldwide. Androgen receptor (AR) signaling is central to PCa and PCa therapy. MicroRNAs (miRNAs) play crucial roles in the regulation of prostate cancer through modulation of signaling pathways. In the present study, we illustrate the functional significance and therapeutic benefit of miR-299-3p, an AR targeting microRNA, in PCa progression. We noted loss of expression of miR-299-3p in prostate tumors compared to noncancerous prostate tissues. Replenishment of miR-299-3p in C4-2B, 22Rv-1 and PC-3 cells contributed to cell cycle arrest, reduced proliferation, migration and increased expression of apoptotic markers. Additionally, overexpression of miR-299-3p induced a reduction of AR, PSA and VEGFA expression. AGO-RNA pulldown experiment showed enrichment of AR, VEGFA and miR-299-3p in C4-2B cells overexpressing miR-299-3p. miR-299-3p overexpression also inhibited epithelial mesenchymal transition, expression of Slug, TGF-?3, phospho-AKT and phospho-PRAS40, but increased expression of E-cadherin. Furthermore, miR-299 overexpression resulted in reduced tumor growth in xenograft models and increased drug sensitivity. Overall, this study has identified novel mechanisms of antitumor and antimigration function of miR-299-3p through modulation of AR and VEGFA signaling pathways which lead to improved drug sensitivity of PCa.
2020-01-01 | S-EPMC7083835 | BioStudies
Project description:Aim:To characterize the miRNA expression profile in head and neck squamous cell carcinoma (HNSSC) accounting for a broad range of cancer subtypes and consequently identify an optimal miRNA signature with prognostic value. Background:HNSCC is consistently among the most common cancers worldwide. Its mortality rate is about 50% because of the characteristic aggressive behavior of these cancers and the prevalent late diagnosis. The heterogeneity of the disease has hampered the development of robust prognostic tools with broad clinical utility. Materials and methods:The Cancer Genome Atlas HNSC dataset was used to analyze level 3 miRNA-Seq data from 497 HNSCC patients. Differential expression (DE) analysis was implemented using the limma package and multivariate linear model that adjusted for the confounding effects of age at diagnosis, gender, race, alcohol history, anatomic neoplasm subdivision, pathologic stage, T and N stages, and vital status. Random forest (RF) for survival analysis was implemented using the randomForestSRC package. Results:A characteristic DE miRNA signature of HNSCC, comprised of 11 upregulated (i.e., miR-196b-5p, miR-1269a, miR-196a-5p, miR-4652-3p, miR-210-3p, miR-1293, miR-615-3p, miR-503-5p, miR-455-3p, miR-205-5p, and miR-21-5p) and 9 downregulated (miR-376c-3p, miR-378c, miR-29c-3p, miR-101-3p, miR-195-5p, miR-299-5p, miR-139-5p, miR-6510-3p, miR-375) miRNAs was identified. An optimal RF survival model was built from seven variables including age at diagnosis, miR-378c, miR-6510-3p, stage N, pathologic stage, gender, and race (listed in order of variable importance). Conclusions:The joint differential miRNA expression and survival analysis controlling for multiple confounding covariates implemented in this study allowed for the identification of a previously undetected prognostic miRNA signature characteristic of a broad range of HNSCC.
2018-01-01 | S-EPMC5698002 | BioStudies
Project description:Increasing evidence has demonstrated that microRNAs (miRNAs) are involved in colon cancer initiation and progression, and may serve as diagnostic and prognostic biomarkers for colon cancer. Here, we investigated the levels of miR-9-1, miR-203-3p, miR-221-3p, miR-342-3p, miR-491-5p and miR-503-5p in 90 pairs of colon cancer and adjacent normal tissues, and explored the relationship between their expression and clinical outcome of colon cancer. Five miRNAs (miR-203-3p, miR-221-3p, miR-342-3p, miR-491-5p and miR-503-5p) were dysregulated in colon cancer tissue (P < 0.05). The levels of miR-503-5p in larger tumors (? 6 cm) were higher than those in smaller ones (< 6 cm) (P = 0.031), while the levels of miR-203-3p and miR-491-5p in patients aged 70 years and older were higher than those in patients aged younger than 70 years (P = 0.019 and 0.049, respectively). The high levels of miR-221-3p (HR = 2.416, 95% CI 1.314-4.445, P = 0.005), miR-342-3p (HR = 1.807, 95% CI 1.003-3.253, P = 0.049) and miR-491-5p (HR = 1.868, 95% CI 1.032-3.384, P = 0.039) were significantly associated with worse survival time. Moreover, combination analysis of miR-221-3p, miR-342-3p and miR-491-5p expression revealed that patients with 3 highly expressed miRNAs had lower survival rates compared with those with zero-to-two highly expressed miRNAs (HR = 2.100, 95% CI 1.157-3.813, P = 0.015), especially those with TNM stages I and II (HR = 4.204,95% CI 1.762-10.030, P = 0.001). Our results suggest that the three-miRNA signature may help doctors better predict prognosis and guide treatment decisions for colon cancer.
1000-01-01 | S-EPMC4113501 | BioStudies
Project description:BACKGROUND: Metastasis is the major cause of cancer-related death in patients with gastric cancer, and aberrant expression of various microRNAs (miRNAs) is associated with cancer metastasis. METHODS: Profiling of differentially expressed miRNAs was performed in three cases of primary gastric cancer and the corresponding metastatic lymph node tissues. Then, the five most altered miRNAs were further verified in 16 paired samples. Two of these five miRNAs were further assessed for their effects on the regulation of gastric cancer cell growth and invasion. RESULTS: The miRNA profile data showed 151 upregulated miRNAs (? 1.5-fold) and 285 downregulated miRNAs (? 0.67-fold) in the metastatic tissues compared to the primary gastric cancer tissues. Among these five miRNAs (i.e., hsa-miR-508-5p, hsa-miR-30c, hsa-miR-337-3p, hsa-miR-483-5p, and hsa-miR-134), expression of hsa-miR-337-3p and hsa-miR-134 was significantly downregulated in these 16 lymph node metastatic tissues compared to their primary tumor tissues (P<0.05) and in nine gastric cancer cell lines compared to the nonmalignant GES cell line. Furthermore, induction of hsa-miR-134 or hsa-miR-337-3p expression did not dramatically affect gastric cancer cell proliferation, but transfection of the hsa-miR-337-3p mimic did reduce gastric cancer cell invasion capacity. CONCLUSIONS: These findings indicate that hsa-miR-337-3p plays a role in the reduction of gastric cancer cell invasion capacity, and further studies on the mechanism of hsa-miR-337-3p in gastric cancer metastasis are warranted.
1000-01-01 | S-EPMC3854519 | BioStudies