HOXA5-miR-574-5p axis promotes adipogenesis and alleviates insulin resistance.
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ABSTRACT:
SUBMITTER: Li Y
PROVIDER: S-EPMC8693313 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectiveLong non-coding RNAs (lncRNAs) and microRNAs (miRNAs) play essential roles in the tumour progression. LncRNAs mostly act as competing endogenous RNAs (ceRNAs) by sponging miRNAs. This study aimed to study the association of a novel lncRNA MFI2-AS1 with miR-574-5p/MYCBP axis in the development of colorectal cancer (CRC).MethodsNinety-four CRC tissues and paired adjacent non-tumour tissues were included in our study. The relative expression level of MFI2-AS1 was detected, and its relationship with clinico-pathological factors was analysed. Then, the CRC cells lines (LoVo and RKO) were transfected with MFI2-AS1 siRNA, miR-574-5p mimics and inhibitors. Cell proliferation, migration, invasion, cell cycle distribution and DNA damage in response to different transfection conditions were examined. Dual-luciferase reporter assay was performed to identify the target interactions between MFI2-AS1 and miR-574-5p, miR-574-5p and MYCBP.ResultsLncRNA MFI2-AS1 and MYCBP were up-regulated in CRC tissues when compared with adjacent non-tumour tissues. The expression levels of MFI2-AS1 were significantly associated with tumour histological grade, lymph and distant metastasis, TNM stage and vascular invasion. Both MFI2-AS1 siRNA and miR-574-5p mimics inhibited proliferation, migration and invasion in LoVo and RKO cells. The transfection of miR-574-5p inhibitor showed MFI2-AS1 siRNA-induced changes in CRC cells. Dual-luciferase reporter assay revealed target interactions between MFI2-AS1 and miR-574-5p, miR-574-5p and MYCBP.ConclusionsThese findings suggested that lncRNA MFI2-AS1 and MYCBP have promoting effects in CRC tissues. LncRNA MFI2-AS1 promoted CRC cell proliferation, migration and invasion through activating MYCBP and by sponging miR-574-5p.
| S-EPMC6668983 | biostudies-literature
Project description:BackgroundCircular RNAs (circRNAs) are important regulators on the onset and progression of rheumatoid arthritis (RA). Our purpose is to explore the role and underpin mechanism of circ_0000396 in RA progression.MethodsRA patients (n = 39) and healthy volunteers (n = 33) were recruited from the Affiliated Hospital of Shaanxi University of Chinese Medicine for the present work. Circ_0000396, microRNA-574-5p (miR-574-5p) and R-spondin 1 (RSPO1) RNA levels were analyzed by reverse transcription-quantitative polymerase chain reaction. Cell proliferation was analyzed by 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, colony formation assay, and 5-ethynyl-2'-deoxyuridine (EDU) assay. Cell apoptosis was assessed by flow cytometry. Protein expression levels of proliferating cell nuclear antigen (PCNA), Cyclin D1, Cyclin E1, BCL2-associated × protein (Bax), B-cell lymphoma-2 (Bcl2), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and RSPO1 were detected by western blot assay. Enzyme-linked immunosorbent assay (ELISA) was conducted to analyze the secretion of pro-inflammatory cytokines including IL-1β and TNF-α. The interaction between miR-574-5p and circ_0000396 or RSPO1 was confirmed by dual-luciferase reporter assay and RNA-pull down assay.ResultsCirc_0000396 expression was notably down-regulated in RA patients compared with healthy controls. Circ_0000396 overexpression suppressed the proliferation and inflammatory response and triggered the apoptosis of RA synovial fibroblasts (RASFs), accompanied by decreases in PCNA, Cyclin D1, Cyclin E1, Bcl2, IL-1β and TNF-α protein expression and an increase in Bax protein expression. Circ_0000396 acted as a molecular sponge for miR-574-5p, and circ_0000396 overexpression-mediated protective effects on RASFs dysfunction were largely reversed by the introduction of miR-574-5p mimics. miR-574-5p interacted with the 3' untranslated region (3'UTR) of RSPO1, and miR-574-5p negatively regulated RSPO1 expression in RASFs. Circ_0000396 could up-regulate the expression of RSPO1 by sponging miR-574-5p in RASFs. RSPO1 interference largely overturned circ_0000396 overexpression-mediated effects in RASFs.ConclusionCirc_0000396 restrained the proliferation and inflammation and induced the apoptosis of RASFs by mediating miR-574-5p/RSPO1 axis, which provided novel potential targets for RA treatment.
| S-EPMC10514958 | biostudies-literature
Project description:Osimertinib is a third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) for lung adenocarcinoma (LUAD) harboring activating mutations, but patients ultimately develop acquired resistance. Circular RNAs are involved in EGFR-TKI resistance, while the role of hsa_circ_0005576 in the osimertinib resistance of LUAD remains unknown. In this study, we demonstrated that hsa_circ_0005576 could facilitate osimertinib-resistant LUAD cells. Briefly, knockdown of hsa_circ_0005576 not only suppressed the proliferation and promoted the apoptosis of resistant LUAD cells, but also increased their sensitivity to osimertinib. Mechanistically, hsa_circ_0005576, serving as an miRNA sponge, could directly interact with miR-512-5p and subsequently upregulate the miR-512-5p-targeted insulin-like growth factor 1 receptor. Rescue assays indicated that miR-512-5p inhibition could reverse the effects of hsa_circ_0005576 knockdown in LUAD cells resistant to osimertinib. Overall, our study revealed that hsa_circ_0005576 regulates proliferation and apoptosis through miR-512-5p/IGF1R signaling, which contributes further to the resistance of LUAD cells to osimertinib. In addition, this study provides a novel insight into the mechanisms underlying osimertinib resistance of LUAD.
| S-EPMC8748248 | biostudies-literature
Project description:Thoracic aortic aneurysm (TAA) can lead to fatal complications such as aortic dissection. Since aneurysm dimension poorly predicts dissection risk, microRNAs (miRNAs) may be useful to diagnose or risk stratify TAA patients. We aim to identify miRNAs associated with TAA pathogenesis and that are possibly able to improve TAA diagnosis. MiRNA microarray experiments of aortic media tissue samples from 19 TAA patients and 19 controls allowed identifying 232 differentially expressed miRNAs. Using interaction networks between these miRNAs and 690 genes associated with TAA, we identified miR-574-5p as a potential contributor of TAA pathogenesis. Interestingly, miR-574-5p was significantly down-regulated in the TAA tissue compared to the controls, but was up-regulated in serum samples from a separate group of 28 TAA patients compared to 20 controls (p < 0.001). MiR-574-5p serum levels discriminated TAA patients from controls with an area under the receiver operating characteristic curve of 0.87. In the Fbn1C1041G/+ mouse model, miR-574-5p was down-regulated in aortic tissue compared to wild-type (p < 0.05), and up-regulated in plasma extracellular vesicles from Fbn1C1041G/+ mice compared to wild-type mice (p < 0.05). Furthermore, in vascular smooth muscle cells, angiotensin II appears to induce miR-574-5p secretion in extracellular vesicles. In conclusion, miR-574-5p is associated with TAA pathogenesis and may help in diagnosing this disease.
| S-EPMC6720007 | biostudies-literature
Project description:A growing body of evidence has suggested that circular RNAs (circRNAs) are crucial for the regulation of gene expression and their dysregulation is implicated in several diseases. However, the function of circRNAs in obesity remains largely unexplored. Methods: Global changes in the circRNA expression patterns were detected in adipose tissues derived from obese and lean individuals. In particular, circSAMD4A was identified as significantly differentially upregulated and was functionally analyzed, both in vitro and in vivo, using various approaches. Results: CircSAMD4A overexpression was correlated with a poor prognosis in obese patients. By contrast, circSAMD4A knockdown inhibited differentiation in isolated preadipocytes. In high-fat diet (HFD) -induced obese mice, circSAMD4A knockdown reversed the associated weight gain, reduced food intake, lower body fat, and increased energy expenditure. These mice also exhibited increased insulin sensitivity and glucose tolerance. Furthermore, in vitro experiments indicated that circSAMD4A affected differentiation by binding to miR-138-5p and regulating EZH2 expression. Conclusions: CircSAMD4A regulated preadipocyte differentiation by acting as a miR-138-5p sponge, and thus increasing EZH2 expression. These results suggested that circSAMD4A can serve as a potential target for obesity treatments and/or as a potential prognostic marker for obese patients following bariatric surgery.
| S-EPMC7150479 | biostudies-literature
Project description:BackgroundNon-small cell lung cancer (NSCLC) is the most common tumor with severe morbidity and high mortality. Long non-coding RNAs (lncRNAs) as crucial regulators participate in multiple cancer progressions. However, the role of lncRNA MEG8 in the development of NSCLC remains unclear. Here, we aimed to investigate the effect of lncRNA MEG8 on the progression of NSCLC and the underlying mechanism.MethodsCell proliferation was analyzed by EdU assays. The impacts of lncRNA MEG8, miR-15a-5p, and miR-15b-5p on cell invasion and migration of NSCLC were assessed by transwell assay. The luciferase reporter gene assay was performed using the Dual-luciferase Reporter Assay System. The effect of lncRNA MEG8, miR-15a-5p, and miR-15b-5p on tumor growth was evaluated in nude mice of Balb/c in vivo.ResultsWe revealed that the expression levels of MEG8 were elevated in the NSCLC patient tissues compared to that in adjacent normal tissues. The expression of MEG8 was negatively relative to that of miR-15a-5p and miR-15b-5p in the NSCLC patient tissues. The expression of MEG8 was upregulated, while miR-15a-5p and miR-15b-5p were downregulated in NSCLC cell lines. The depletion of MEG8 inhibited NSCLC cell proliferation, migration, and invasion in vitro. MEG8 contributed to NSCLC progression by targeting miR-15a-5p/miR-15b-5p in vitro. LncRNA MEG8 contributes to tumor growth of NSCLC via the miR-15a/b-5p/PSAT1 axis in vivo. Thus, we concluded that lncRNA MEG8 promotes NSCLC progression by modulating the miR-15a/b-5p/PSAT1 axis.ConclusionsOur findings demonstrated that lncRNA MEG8 plays a critical role in NSCLC development. LncRNA MEG8, miR-15a-5p, miR-15b-5p, and PSAT1 may serve as potential targets for NSCLC therapy.
| S-EPMC7852147 | biostudies-literature
Project description:Circular RNA (circRNA) is a special category of non-coding RNA that has garnered increasing attention in the exploration of lipid metabolism. However, the functional regulation mechanisms of circRNAs in obesity diseases remain unclear. By whole transcriptome sequencing, a total of 164 circular RNAs were found to exhibit differential expression between lean and obese individuals. RT-qPCR was used to detect significant expression of circMAPK9 in obese individuals, and it was closely related to BMI. Western blot, triglyceride detection, and Oil Red O staining were employed to investigate the role of circMAPK9/hsa-miR-1322/FTO in adipogenesis. In adipocytes, the connection between hsa-miR-1322 and circMAPK9 was verified using fluorescence in situ hybridization, luciferase reporter assay, and RNA immunoprecipitation. It was found that circMAPK9 competed for binding hsa-miR-1322 in the cytoplasm, weakening the inhibitory effect on FTO and promoting adipogenesis. Our study revealed the regulatory mechanism and important role of circMAPK9 in the process of adipogenesis.
| S-EPMC10492215 | biostudies-literature
Project description:Background: Hepatoblastoma is a common hepatic tumor occurring in children between 0-5 years. Accumulating studies have shown lncRNA's potential role in distinct cancer progression and development, including hepatoblastoma. SnoRNA host gene 9 (SNHG9) is associated with the progression of distinct human cancers, but, its specific molecular mechanisms in hepatoblastoma is not unknown. Methods: In this study, we estimated SNHG9 expression in hepatoblastoma tissue and cell lines by quantitative Real-Time Polymerase Chain Reaction (qRT-PCR). Next, we downregulated and upregulated SNHG9 expression in hepatoblastoma cell lines and then determined cell proliferation (CCK-8), colony formation, and cellular apoptosis activity. The dual luciferase reporter activity, RNA immunoprecipitation (RIP), biotin RNA pull down and Spemann's Pearson correlation coefficient assay were performed to establish the interaction between SNHG9, WNt3a and miR- 23a-5p. A xenograft in-vivo tumorgenicity test was performed to elucidate the role of SNHG9 hepatoblastoma in tumorigenesis. SNHG9 role in Cisplatin drug resistance in hepatoblastoma was also determined. Results: SNHG9 was significantly upregulated in hepatoblastoma tissue and cell lines. SNHG9 overexpression on HUH6 & HepG2 resulted in a significant increase in cell proliferation and clonogenic activity while SNHG9 knock down resulted in a sustained inhibition of cell proliferation and clonogenic activity. Dual luciferase activity, RNA immunoprecipitation and biotin pull down confirmed the direct interaction of miR-23a-5p with SNHG9. The xenograft tumorgenicity test showed SNHG9 downregulation significantly inhibited the tumor growth in BALB/c mice. ROC and Kaplan-Meier analysis showed potential prognostic and diagnostic importance of SNHG9 in hepatoblastoma. Conclusion: We concluded that SNHG9/miR-23a-5p/Wnt3a axis promotes the progression hepatoblastoma tumor.
| S-EPMC8425203 | biostudies-literature
Project description:BACKGROUND:Circular RNAs (circRNAs) have been associated with bladder cancer (BC), but the specific underlying molecular mechanism of their association with BC development has not been fully explored. METHODS:Levels of Circ_0008532, MTGR1 and miR-155-5p/miR-330-5p in bladder cancer cell lines and tissues were determined with quantitative real-time PCR and western blotting assays. In vitro and in vivo assays were performed to investigate the function of circ_0008532 in tumorigenesis in bladder cancer cells. The relationships of Circ_0008532, MTGR1 and miR-155-5p/miR-330-5p were predicted using bioinformatic tools and verified by RNA-FISH, RIP and luciferase assays. The effects of circ_0008532 on the Notch signaling pathway were determined by GSEA analysis and western blotting assay. RESULTS:We found that circ_0008532 is upregulated in BC cell lines and tissues. Moreover, overexpression of circ_0008532 promotes, and silencing of circ_0008532 inhibits the capacity for invasive in BC cells. In addition, circ_0008532 can directly interact with miR-155-5p and miR-330-5p as an miRNA sponge which mediates the expression of the miR-155-5p/miR-330-5p target gene MTGR1 and downstream Notch signaling. CONCLUSIONS:Circ_0008532 may act as an oncogene in BC through a novel circ_0008532/miR-155-5p, miR-330-5p /MTGR1/Notch pathway axis, which in turn may provide potential biomarkers and a therapeutic target for the management of bladder cancer.
| S-EPMC7251916 | biostudies-literature
Project description:Endosomal single-stranded RNA-sensing Toll-like receptor-7/8 (TLR7/8) plays a pivotal role in inflammation and immune responses and autoimmune diseases. However, the mechanisms underlying the initiation of the TLR7/8-mediated autoimmune signaling remain to be fully elucidated. Here, we demonstrate that miR-574-5p is aberrantly upregulated in tissues of lupus prone mice and in the plasma of lupus patients, with its expression levels correlating with the disease activity. miR-574-5p binds to and activates human hTLR8 or its murine ortholog mTlr7 to elicit a series of MyD88-dependent immune and inflammatory responses. These responses include the overproduction of cytokines and interferons, the activation of STAT1 signaling and B lymphocytes, and the production of autoantigens. In a transgenic mouse model, the induction of miR-574-5p overexpression is associated with increased secretion of antinuclear and anti-dsDNA antibodies, increased IgG and C3 deposit in the kidney, elevated expression of inflammatory genes in the spleen. In lupus-prone mice, lentivirus-mediated silencing of miR-574-5p significantly ameliorates major symptoms associated with lupus and lupus nephritis. Collectively, these results suggest that the miR-574-5p-hTLR8/mTlr7 signaling is an important axis of immune and inflammatory responses, contributing significantly to the development of lupus and lupus nephritis.
| S-EPMC11000404 | biostudies-literature