BMC CANCER
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2021
·Vol. 21
·期 1
·1-14
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IF 4.43
Shi Yue,Liu Chong
Background Breast cancer (BC) is one of the major malignancies worldwide. Circular ribonucleic acids (circRNAs) are a class of conserved ribonucleic acid (RNA) molecules that play important roles in various diseases. Recently, circRNAs have been suggested to have diagnostic value and may function as potential diagnostic biomarkers for BC. Previously, hsa_circ_0043278 was found to be downregulated in human BC. However, its role in human BC has not yet been identified.Methods The levels of hsa_circ_0043278 in BC cell lines were verified by quantitative reverse transcription–polymerase chain reaction (qRT–PCR). The overexpression vector and short hairpin RNA (shRNA) of hsa_circ_0043278 were transfected into MDA-MB-231 and MCF-7 cells, respectively. The effects of hsa_circ_0043278 on tumour cell growth, migration and invasion were measured by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT), colony formation, wound healing and Transwell assays in vitro. A xenograft experiment was conducted to validate the inhibitory effect of hsa_circ_0043278 on tumour growth. The interaction between hsa_circ_0043278 and miR-455-3p was confirmed by a dual-luciferase reporter assay. Mimics and inhibitors of miR-455-3p were designed to confirm the influence of hsa_circ_0043278 on the hsa_circ_0043278/miR-455-3p/etoposide-induced gene 24 (EI24) axis.Results Hsa_circ_0043278 was downregulated in BC cell lines. Furthermore, overexpression of hsa_circ_0043278 notably decreased BC cell viability and inhibited BC cell migration and invasion in vitro and suppressed tumour growth in vivo. Downregulation of hsa_circ_0043278 led to the opposite results. Hsa_circ_0043278 expression was negatively correlated with that of miR-455-3p. In addition, mechanistic investigation proved that hsa_circ_0043278 directly bound to miR-455-3p and regulated EI24 and NF-κB expression in BC cells.Conclusion Hsa_circ_0043278 acts as a tumour suppressor gene in BC through the hsa_circ_0043278/miR-455-3p/EI24 axis and may be regarded as a new prognostic predictor or potential therapeutic target in BC.
研究领域:
肿瘤学
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分子生物学
·
遗传学
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DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF MEDICAL RESEARCH
·
2024
·Vol. 29
·期 1
·1-14
·
IF 2.8
Zhang Peng,Liu Jie,Chai Zijia,Fu Jinjin,Li Shuwen,Yang Zhe
Background Circular RNAs (circRNAs) are involved in the progression of osteoporosis; however, their impact on osteogenic differentiation has yet to be fully elucidated. In this study, we identified a novel circRNA known as circZfp644-205 and investigated its effect on osteogenic differentiation and apoptosis in osteoporosis. Methods CircZfp644-205, miR-445-3p, and SMAD2 levels were measured using quantitative real-time polymerase chain reaction (qRT-PCR). MC3T3-E1 cells were subjected to microgravity (MG) to establish a cell model. Osteogenic differentiation was assessed using qRT-PCR, Alizarin Red S staining, alkaline phosphatase staining, and western blot. The apoptosis was evaluated using flow cytometry. The relationship between miR-445-3p and circZfp644-205 or SMAD2 was determined using bioinformatics, RNA pull-down, and luciferase reporter assay. Moreover, a hindlimb unloading mouse model was generated to investigate the role of circZfp644-205 in vivo using Micro-CT. Results CircZfp644-205 expression was up-regulated significantly in HG-treated MC3T3-E1 cells. Further in vitro studies confirmed that circZfp644-205 knockdown inhibited the osteogenic differentiation and induced apoptosis of pre-osteoblasts. CircZfp644-205 acted as a sponge for miR-455-3p, which reversed the effects of circZfp644-205 on pre-osteoblasts. Moreover, miR-455-3p directly targeted SMAD2, thus inhibiting the expression of SMAD2 to regulate cellular behaviors. Moreover, circZfp644-205 alleviated the progression of osteoporosis in mice. Conclusions This study provides a novel circRNA that may serve as a potential therapeutic target for osteoporosis and expands our understanding of the molecular mechanism underlying the progression of osteoporosis.
研究领域:
分子生物学
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细胞生物学
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骨质疏松症研究
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
ANALYTICAL LETTERS
·
2021
·
IF 2.329
Yaxin Guo,Dan Liu,Qing Yang,Wei Shi,Zhihui Yang,Jia Chen,Juan Xiang
Serum miR-501-3p and miR-455-3p are potential biomarkers for the diagnosis of Alzheimer’s disease (AD). The combination of both microRNAs (miRNAs) is anticipated to improve AD diagnostic accuracy and provide stage information. In this work, simultaneous determination of both miRNAs was performed using a dual-signal DNA probe based on the fluorescent recovery of carbon quantum dots (CQDs) and the sulfo-cyanine5 (Cy5) dye. Duplex specific nuclease was introduced to amplify the signals via a DNA degradation/RNA re-hybridization cycle. The dynamic ranges of the method were 0.01 to 4 pM for miR-501-3p and 0.01 to 5 pM for miR-455-3p. The accuracy of the method was confirmed by the recoveries of the miRNAs in spiked human serum and high correlation with measurements by the real-time quantitative reverse transcription–polymerase chain reaction (qRT-PCR). The concentrations of the miRNAs were determined in serum from healthy donors and AD patients in preclinical and mild stages. Detailed t-test analysis revealed that despite of the poor correlations of independent miR-501-3p and miR-455-3p with AD progression, the concentration ratio of miR-501-3p to miR-455-3p was significantly correlated with AD diagnosis (p < 0.001 between preclinical AD and healthy control) and early progression (p < 0.001 between preclinical and mild-stage AD). A simple, sensitive method is reported for the simultaneous determination of the miRNAs in serum with high accuracy and shows that the concentration ratio of miR-501-3p to miR-455-3p is an effective blood index for early and in-stage diagnosis of AD.
研究领域:
生物化学
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分子生物学
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神经科学
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诊断医学
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产品关联
DOI
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2025
·
IF 19
Dianbo Long,Guping Mao,Hongyi Li,Huaiwen Chen,Rui Huang,Tianyu Zhao,Zhiqi Zhang,Xiaoyi Zhao
Knee osteoarthritis (KOA) is a common joint disorder characterized by progressive cartilage degeneration. MiR-455-3p has been identified as a promising therapeutic candidate to maintain cartilage homeostasis. However, clinical application of free miR-455-3p is limited by rapid degradation, poor targeting efficiency, and off-target effects. To overcome these limitations, an injectable nanocomposite hydrogel-based miRNA delivery system consisting of a cartilage affinity nanocarrier (CANC) encapsulated within a PCL-b-PEG-b-PCL hydrogel is developed. The CANC is formulated using 50% PEGylated G5 PAMAM dendrimers to load miR-455-3p and is further modified with chondrocyte-affinity peptides (CAP) and minimal “self” peptides (MSP) to enhance cartilage targeting and evade macrophage uptake. In vitro studies demonstrated that it exhibited excellent stability, low cytotoxicity, superior cartilage penetration and chondrocyte targeting. Moreover, in vivo experiments in miR-455-3p knockout mice and a destabilization of the medial meniscus (DMM) induced KOA model confirmed that the sustained release and targeted delivery of miR-455-3p effectively rescued cartilage degeneration and prevent KOA progression. Notably, the nanocomposite hydrogel demonstrated high biocompatibility without observed cytotoxicity in major organs. This study highlights the therapeutic potential of the nanocomposite hydrogel miRNA delivery system in promoting cartilage regeneration and presents a promising approach for the development of disease-modifying osteoarthritis drugs.
研究领域:
医学
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生物材料学
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分子生物学
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产品关联
DOI
高影响因子
Journal of Materials Chemistry B
·
2025
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IF 5.7
Mao Li,Xu Zhang,Lin-han Zhang,Jia-rong Wang,Hua-yang Fan,Zhi-chao Dou,Xin-hua Liang,Ya-ling Tang
Postoperative salivary adenoid cystic carcinoma (SACC) without symptoms is marked by dormant tumor cells in the primary site and metastatic organs. These cells, when reactivated, cause recurrence and metastasis. A treatment strategy that targets the “awakening” and elimination of these cells, combined with chemotherapy, could prevent and treat recurrence and metastasis. High expression of miR-455-3p were found to be crucial for SACC cell dormancy induced by serum starvation. High expression of miR-455-3p was inversely correlated with Ki-67 levels, while its reduction was linked to SACC tumor recurrence. These findings further imply that elevated miR-455-3p expression in SACC is indicative of a state of tumor dormancy. Mechanistically, a dual luciferase reporter assay provided further validation that miR-455-3p targeted GNPNAT1, regulating SACC dormancy. GNPNAT1 is downregulated in SACC tissues, and its overexpression inhibits cell dormancy and migration/invasion. An injectable, thermosensitive hydrogel designed to deliver antagomiR-455-3p via paclitaxel liposomes formed a Lip@miR hydrogel. This hydrogel “awakened” dormant SACC cells, suppressing their tumorigenic potential and leading to their eradication through sustained paclitaxel release in vivo. This approach presents a new therapeutic strategy for eliminating dormant tumor cells and reducing the risk of post-therapy cancer relapse.
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产品关联
DOI
PubMed
高影响因子
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