CircRFWD3 promotes HNSCC metastasis by modulating miR-27a/b/PPARγ signaling
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ABSTRACT:
PROVIDER: PRJNA827696 | ENA |
REPOSITORIES: ENA
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Project description:Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer in the world. Its mortality rate is high, and metastasis is one of the main reasons for the poor prognosis. Therefore, it is quite urgent to elucidate the mechanism of HNSCC metastasis and to discover valuable therapeutic targets. Circular RNAs (circRNAs) have been characterized as key regulators of gene expression in numerous malignances. However, the role of circRNAs in HNSCC metastasis remains largely unknown. In this study, circRFWD3, was defined. We demonstrated a novel circRNA, circRFWD3, was significantly upregulated in HNSCC tissues and cell lines by circRNA microarray analysis and qPCR. Notably, high expression of circRFWD3 is related to highly aggressive HNSCC cell lines and lymph node metastasis in HNSCC patients. After that, Sanger sequencing, RNase R and actinomycin D assay were performed to verify the ring structure of circRFWD3. Then functional experiments found it could promote the metastasis of HNSCC cells both in vitro and in vivo. Mechanistically, dual luciferase reporter assay, FISH, RIP, RNA pull-down, RNA-seq and western blot experiments were employed, and found that circRFWD3 served as a miRNAs sponge for miR-27a/27b, leading to upregulation of PPARγ, and then activate NF-κB/MMP13 signaling. Finally, ISH and IHC were carried out to determine the expression levels and clinical significances of circRFWD3 and PPARγ in clinical cohorts of HNSCC. According to the analysis results from two independent HNSCC cohorts, upregulated expression of circRFWD3 and PPARγ were positively associated with worse survival in patients with HNSCC. Overall, our results uncover that circRFWD3 acts a critical role in promoting the aggressiveness of HNSCC cells and is a prognostic marker for the disease, indicating that circRFWD3 may act as a potential therapeutic target in HNSCC. CircRNA microarray analysis of HNSCC
2023-11-29 | GSE200946 | GEO
Project description:Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer in the world, the 5-year survival rate of patients with HNSCC is still about 50% due to frequent metastasis and recurrence. Circular RNAs (circRNAs) have been characterized as key regulators of gene expression in numerous malignancies. However, the role of circRNA in HNSCC metastasis remains largely unknown. Here, we demonstrated that the circRFWD3 was significantly upregulated in HNSCC tissues and cell lines by circRNA microarray analysis and qPCR. Notably, high expression of circRFWD3 is related to highly aggressive HNSCC cell lines and lymph node metastasis in HNSCC patients. After that, Sanger sequencing, RNase R, and actinomycin D assay were performed to verify the ring structure of circRFWD3. Then functional experiments found it could promote the metastasis of HNSCC cells both in vitro and in vivo. Mechanistically, a dual-luciferase reporter assay, FISH, RIP, RNA pull-down, RNA-seq, and western blot experiments were employed and found that circRFWD3 served as a miRNAs sponge for miR-27a/27b, leading to the upregulation of PPARγ, and then promoted HNSCC metastasis via NF-κB/MMP13 pathway. Finally, ISH and IHC were carried out to determine the expression levels and clinical significances of circRFWD3 and PPARγ in clinical cohorts of HNSCC. According to the analysis results from two independent HNSCC cohorts, upregulated expression of circRFWD3 and PPARγ were positively associated with worse survival in patients with HNSCC. Overall, our results uncover that circRFWD3 acts a critical role in promoting the aggressiveness of HNSCC cells and is a prognostic marker for the disease, indicating that circRFWD3 may act as a potential therapeutic target in HNSCC.
| S-EPMC9188624 | biostudies-literature
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2014-12-31 | GSE40410 | GEO
Project description:Microarry analysis of mouse gene expression profile after transfected with miR-27a mimics (27a-7) and mimic NC (NC-9) Goal was to determine the effects of miR-27a transfection on global gene expression. Two-condition experiment, 27a-7 vs.NC-9.
2013-01-31 | E-GEOD-43910 | biostudies-arrayexpress
Project description:Microarry analysis of mouse gene expression profile after transfected with miR-27a mimics (27a-7) and mimic NC (NC-9) Goal was to determine the effects of miR-27a transfection on global gene expression.
2013-01-31 | GSE43910 | GEO
Project description:In infection with an adenovirus, it remains to be clarified whether host miRNAs affect Ad replication. We focused on miR-27 as an miRNA crucial for regulation of Ad infection because miR-27 has been reported to be involved in infection of other viruses, including MCMV and herpesvirus saimiri (HVS). We used microarrays to detail gene expression profiles in miR-27a/b-overexpressing HeLa cells and demonstarted that expression levels of various genes were down- or up-regulated following transfection with miR-27a/b mimics.
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Project description:Comparison af adherent growing breast cancer cell lines versus mammospheres under serum-free conditions Background: In patients with breast cancer, subsets of long-lived cells tolerate chemotherapies. These chemoresistant cells can remain dormant at secondary sites, such as bone and lung, for years and decades. Cancer cells endowed with drug resistance are maintained in vivo in a quiescent slow-growing state that preserves them from anti-proliferative cancer drugs. The mechanism of conversion from dormancy to growth remains poorly understood. We aimed to identify microRNAs (miRNAs) as master regulators of cancer stem cells (CSCs) maintainance, because one of the characteristics of CSCs is their slow proliferation or dormancy. MiRNA targeting CSCs may be an effective therapy to improve the prognosis of breast cancer patients. Methods: We performed miRNA array analysis to identify differences miRNA expression profiles between adherent cells and mammospheres that contain higher number of breast cancer stem cells (BCSCs). In this approach, we focused on expression of hsa-miR-27a. Further, roles of hsa-miR-27a target genes in maintaining BCSC properties were analysed . Results: Here, we showed that hsa-miR-27a was downregulated in mammosphere cells. The formation of BCSCs was attenuated by transfection of hsa-miR-27a. We found that hsa-miR-27a targets F-box and WD-40 domain protein 7 (FBW7), a tumor suppressor gene, thereby inducing tumor dormancy. Additionally, we found that hsa-miR-27a targets genes involved in GSH synthesis, including xCT (encoded by SLC7A11), a heterodimeric protein of a transporter subunit of the xC(-) system, cystathionine gamma-lyase (CTH/CSE), and nuclear factor-erythroid 2-related factor 2 (Nrf2/NFE2L2), thereby increasing intracellular reactive oxygen species (ROS) levels. Upregulation of these genes by antisense (as)-miR-27a induced autophagy. Conclusions: Previous studies showed that expression of hsa-miR-27a is elevated in breast cancer. Here, we showed that expression of hsa-miR-27a was reduced in BCSC. CSCs in the dormant state are resistant to chemotherapy due to inhibition of ROS accumulation in these cells. These results demonstrate that hsa-miR-27a plays an essential role in maintaining the BCSCs phenotype via regulation of FBW7, ROS related genes and the Nrf2 pathway, as well as in the dormant-to-proliferative switch of breast cancer cells. Thus, hsa-miR-27a represents a novel strategy for various type of breast cancer.
2019-03-06 | GSE127849 | GEO
Project description:Pancreatic β-cell dysfunction caused by obesity can be associated with alterations in the levels of microRNAs (miRNAs). However, the role of miRNAs in such processes remains elusive. Here, we show that pancreatic islet miR-27a-5p, which is markedly increased in obese mice and impairs insulin secretion, is mainly delivered by visceral adipocyte-derived extracellular vesicles (EVs). Depleting miR-27a-5p significantly improves insulin secretion and glucose intolerance in db/db mice. Supporting the function of EVs’ miR-27a-5p as a key pathogenic factor, intravenous injection of miR-27a-5p-containing EVs shows their distribution in mouse pancreatic islets. Tracing the injected AAV-miR-27a-5p (AAV-miR-27a) or AAV-FABP4-miR-27a-5p (AAV-FABP4-miR-27a) in visceral fat results in upregulating miR-27a-5p in EVs and serum, and elicits mouse pancreatic β-cell dysfunction. Mechanistically, miR-27a-5p directly targets L-type Ca2+ channel subtype CaV1.2 (Cacna1c) and reduces insulin secretion in β-cells. Overexpressing mouse CaV1.2 largely abolishes the insulin secretion injury induced by miR-27a-5p. These findings reveal a causative role of EVs’ miR-27a-5p in visceral adipocyte-mediated pancreatic β-cell dysfunction in obesity-associated type 2 diabetes mellitus.
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