MOLECULAR HUMAN REPRODUCTION
·
2023
·Vol. 29
·期 11
·
IF 4
Fan Hairui,Zhou Dongjie,Zhang Xiaomei,Jiang Min,Kong Xiang,Xue Tongmin,Gao Lingling,Lu Dan,Tao Chenyue,Wang Liping
Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disease that affects women of reproductive age. It is also a significant cause of infertility. Circular RNAs have been found to have a crucial role in the development and progression of reproductive system diseases. In this study, we focused on circ_BECN1 and aimed to investigate its role and mechanism in PCOS, providing a foundation for early diagnosis and treatment of this condition. Our findings revealed an upregulation of circ_BECN1 expression in the ovarian granulosa cells (GCs) of PCOS patients. Additionally, the silencing of circ_BECN1 resulted in inhibited proliferation and enhanced apoptosis of the human ovarian granulosa-like tumor cell line (KGN), therefore implicating circ_BECN1 in the cell cycle process. Through a dual-luciferase reporting assay, we determined that circ_BECN1 acts as a sponge for miR-619-5p and that Rab5b is the target gene of miR-619-5p. Moreover, the expression of Rab5b was found to be upregulated in the ovarian tissue of PCOS patients. Knocking down circ_BECN1 resulted in decreased Rab5b expression, which was then restored by using a miR-619-5p inhibitor. Additionally, rescue experiments demonstrated that overexpressing Rab5b reversed the effects of circ_BECN1 knockdown on cell proliferation and apoptosis in KGN cells. In summary, our findings indicate that circ_BECN1 is upregulated in PCOS GCs and promotes cell growth and cell cycle progression, and reduces cell apoptosis by modulating the miR-619-5p/Rab5b axis. Therefore, circ_BECN1 may serve as a potential therapeutic target for PCOS treatment.
研究领域:
生殖内分泌学
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分子生物学
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妇科学
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产品关联
DOI
PubMed
高影响因子
TOXICOLOGY LETTERS
·
2023
·
IF 3.5
Yizhou Zhong,Bingli Zhang,Yuji Huang,Jiaxin Du,Boxuan Liang,Zhiming Li,Rongyi Ye,Bo Wang,Hongyi Xian,Xifei Yang,Weifeng Rong,Xiang Guo,Xingfen Yang,Zhenlie Huang
1,2-Dichloroethane (1,2-DCE) is a pervasive environmental pollutant found in ambient and residential air, as well as ground and drinking water . Brain edema is the primary pathological consequence of 1,2-DCE overexposure. We found that microRNA (miRNA)-29b dysregulation after 1,2-DCE exposure can aggravate brain edema by suppressing aquaporin 4 (AQP4). Moreover, circular RNAs (circRNAs) can regulate the expression of downstream target genes through miRNA , and affect protein function. However, circRNAs’ role in 1,2-DCE-induced brain edema via miR-29b-3p/AQP4 axis remains unclear. To address the mechanism’s bottleneck, we explored the circRNA-miRNA-mRNA network underlying 1,2-DCE-driven astrocyte swelling in SVG p12 cells by circRNA sequencing, electron microscopy and isotope 3 H labeling combined with the 3-O-methylglucose uptake method. The results showed that 25 and 50 mM 1,2-DCE motivated astrocyte swelling, characterized by increased water content, enlarged cell vacuoles, and mitochondrial swelling. This was accompanied by miR-29b-3p downregulation and AQP4 upregulation. We verified that AQP4 were negatively regulated by miR-29b-3p in 1,2-DCE-induced astrocyte swelling. Also, circRNA sequencing highlighted that circBCL11B was upregulated by 1,2-DCE. This was manifested as circBCL11B overexpression playing an endogenous competitive role via upregulating AQP4 by binding to miR-29b-3p, thus leading to astrocyte swelling. Conversely, circBCL11B knockdown reversed the 1,2-DCE-motivated AQP4 upregulation and alleviated the cell swelling. Finally, we demonstrated that the circBCL11B was targeted to miR-29b-3p by fluorescence in situ hybridization and dual-luciferase reporter assay. In conclusion, our findings indicate that circBCL11B acts as a competing endogenous RNA to facilitate 1,2-DCE-caused astrocyte swelling via miR-29b-3p/AQP4 axis. These observations provide new insight into the epigenetic mechanisms underlying 1,2-DCE-induced brain edema.
研究领域:
毒理学
·
神经科学
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分子生物学
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细胞生物学
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DOI
PubMed
高影响因子
INTERNATIONAL DENTAL JOURNAL
·
2025
·
IF 3.7
Xiaolan Guo,Kailun Wu,Longrui Dang,Sitong Liu,Jing Xu,Runting Wang,Junyang Xu,Yiming Zhong,Zhao Chen,Buling Wu
Background Pulpitis is an oral disease primarily triggered by microbial infections. Current therapeutic strategies lack specific agents targeting the underlying pathogenic mechanisms. Non-coding RNAs (ncRNAs) and their competitive endogenous RNA (ceRNA) networks have emerged as critical regulators of diverse biological processes, offering novel insights into the pathogenesis of pulpitis and the identification of potential therapeutic targets. Methods RNA sequencing was performed on pulp tissues from healthy individuals and pulpitis patients. Bioinformatics tools were employed to analyse sequencing data, identify differentially expressed messenger RNAs (mRNAs), and construct protein-protein interaction (PPI) networks to pinpoint hub genes. A murine pulpitis model was established to investigate the effects of neutrophil extracellular trap (NET) inhibitors on disease progression. A NET-associated ceRNA regulatory network was systematically constructed based on ceRNA theory. In vitro experiments validated the expression patterns of key ncRNAs and mRNAs in pulpitis. Results Differentially expressed mRNAs, long non-coding RNAs (lncRNAs), and Circular RNAs (circRNAs) were identified in pulpitis. Bioinformatics analysis revealed significant activation of NET-related pathways, with sialic acid-binding immunoglobulin-like lectin-9 (SIGLEC9), complement C3 (C3), H2A clustered histone 14 (H2AC14), and H4 clustered histone 11 (H4C11) identified as core regulatory genes. In vivo experiments demonstrated that NET inhibition alleviated dental pulpitis and necrosis. Furthermore, a novel NET-associated ceRNA regulatory network was established, revealing four critical regulatory axes: LINC00466 / hsa-miR-27a-3p / SIGLEC9, hsa_circDNAH11_003 / hsa-miR-877-5p / C3, hsa_circSLC15A4_001 / hsa-miR-30d-3p / H2AC14, and hsa_circGABBR2_009 / hsa-miR-193b-3p / H4C11. These ncRNAs exhibited significant upregulation in inflamed pulp tissues. Conclusion By constructing a comprehensive NET-associated ceRNA network, we elucidate molecular mechanisms underlying dental pulpitis, providing novel evidence for understanding the disease progression. These findings establish a theoretical foundation for developing targeted therapeutic strategies against pulpitis.
研究领域:
口腔医学
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分子生物学
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免疫学
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生物信息学
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遗传学
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转录组学
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病理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
AIP Advances
·
2025
·Vol. 15
·期 7
·
IF 1.4
Yu Dong-hua,Wang Yu,Yu Chun-Miao,Zhou Qi,Liu Shu-min,Liu Ting-ting
The aim of this study is to construct a competitive endogenous RNA regulatory network of gouty arthritis through transcriptomics and investigate its underlying pathogenesis. Transcriptomics was performed with the rats’ joints in both the control and model groups. The mRNA, miRNA, lncRNA, and circRNA were analyzed using the R language. The RNA data were visualized as the ceRNA network. Genes were combined, the KEGG pathway was enriched, and the first five pathways were selected. Meanwhile, relationships between genes in the extraction pathway were integrated into a network, and key genes were mapped. mRNA, lncRNA, and circRNA were scored to compare the conservatism of RNA. Finally, lncRNA, circRNA, miRNA, and genes were considered the core, and information about other differential RNAs having a targeted relationship with them (i.e., host genes) was added. Based on ceRNA analysis, the relationship pairs between lncRNA–miRNA–mRNA and circRNA–miRNA–mRNA were extracted. A total of 1165 de-mRNAs, 91 de-miRNAs, 456 de-lncRNAs, and 70 de-circRNAs were selected. The key genes were identified for pathway enrichment, such as the phospholipase D signaling pathway and endocytosis. Based on the ceRNA analysis, the networks of lncRNA–miRNA–mRNA and circRNA–miRNA–mRNA were constructed. The differentially expressed RNAs between the control and model groups were identified using the transcriptomics of ankle tissue. The findings indicate that mRNA, lncRNA, and circRNA can competitively bind to GA-related miRNAs, leading to mutual regulatory effects. The RNAs identified from the constructed lncRNA–miRNA–mRNA and circRNA–miRNA–mRNA networks are potential targets for therapeutic drugs and may be involved in the pathogenesis of GA.
研究领域:
分子生物学
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基因组学
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生物信息学
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RNA生物学
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免疫学
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关节炎研究
✓ 已验证
产品关联
DOI
高影响因子
Journal of Ocean University of China
·
2024
·Vol. 23
·期 6
·1615-1629
·
IF 1.4
Wang Wenwen,Wei Shu,Chen Yadong,Tan Suxu,Shi Kunpeng,Zang Shaoqing,Wang Minmin,Yang Teng,Yang Yingming,Cui Zhongkai,Sha Zhenxia
As an efficient immunostimulant, chitosan oligosaccharide (COS) can enhance the immunity of teleosts; however, the underlying molecular mechanisms still require elucidation. Competing endogenous RNAs (ceRNAs) are vital regulators in the immune response, but their roles in half-smooth tongue sole ( Cynoglossus semilaevis ) remain unclear. In this study, for the first time, we studied whole-transcriptome expression profiles and analyzed ceRNA networks in peripheral blood leukocytes of half-smooth tongue sole treated with COS. A total of 19 circRNAs (DE-circRNAs), 18 miRNAs (DE-miRNAs) and 50 previously identified lncRNAs (DE-lncRNAs) were differentially expressed after COS stimulation. The DE-lncRNAs and DE-miRNAs targeted numerous immunity-related genes, and were enriched in important pathways, including MAPK and Toll-like receptor signaling pathways, suggesting the immunoregulatory roles of COS. Furthermore, we constructed circRNA-miRNA-mRNA and lncRNA-miRNA-mRNA regulatory networks using DE-circRNAs, DE-miRNAs, DE-lncRNAs, and DE-mRNAs. Additionally, a ceRNA network with immunity-related DE-mRNAs was constructed, showing that 3 DE-circRNAs, 12 DE-lncRNAs, and 29 DEGs exhibited crosstalk through 9 DE-miRNAs. Intriguingly, a DE-miRNA in the ceRNA network, miR-144-3p, was targeted by DE-lncRNA tnrc6a , and negatively regulated the genes of inhibitor of nuclear factor kappa B kinases (IKKs) ( ikbkg , ikbkb , and ikbip ) and c3ar1 . Ikbkg , ikbkb , and c3ar1 were significantly up-regulated in macrophages stimulated by LPS. It could be inferred that ncRNAs participated in the immune and inflammatory response by acting as ceRNAs after COS stimulation in teleosts. These findings indicate that COS could enhance the immunity of teleosts by regulating ncRNAs, and lay the foundation for further practical application of COS in aquaculture.
研究领域:
免疫学
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分子生物学
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水产养殖
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转录组学
✓ 已验证
DOI
高影响因子
Cells
·
2023
·Vol. 12
·期 6
·831
·
IF 6
Xuehui Wang,Jiaying Wang,Zihui An,Aifen Yang,Mengsheng Qiu,Zhou Tan
Mounting evidence suggests that circular RNAs play important roles in the development and progression of cancers. However, their function in glioblastomas (GBM) is still unclear. By circRNA array analysis, we found that circXPO1 (hsa_circ_102737) was significantly upregulated in GBM, and qPCR analysis verified that the circXPO1 expression level was increased in both GBM tissues and cell lines. Functional studies demonstrated that the knockdown of circXPO1 in GBM cell lines repressed cell proliferation and migration; conversely, the overexpression of circXPO1 promoted the malignancy of GBM cells. In line with these findings, circXPO1 inhibition effectively suppressed gliomagenesis in the in situ transplantation model of nude mice. Through bioinformatic analyses and dual-luciferase reporter assays, we showed that circXPO1 directly bound to miR-7-5p, which acted as a tumor suppressor through the negative regulation ofRAF1. In conclusion, our studies suggest that the circXPO1/miR-7-5p/RAF1axis promotes brain tumor formation and may be a potential therapeutic target for GBM treatment.Keywords:circXPO1;glioblastomas;ceRNA;miR-7-5p;RAF1
研究领域:
肿瘤学
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分子生物学
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神经科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2022
·
IF 3.322
Weimin Lin,Xianyu Wen,Xuexin Li,Lei Chen,Wei Wei,Lifan Zhang,Jie Chen
CeRNA effect was an important regulation mode of miRNA mediated bio-activities, however, most of the researches of ceRNA were on ncRNAs synergetic with mRNAs, the exploration of ceRNA effect regulated mRNA interaction was still lack of. Besides, C/EBPα was one of the most crucial adipogenic regulators, which has been demonstrated to form a protein complex with FOXO1 to mediate AdipoQ expression. So that, we try to explore whether the ceRNA effect mediated the interaction of C/EBPα and FOXO1, and identified the key miRNAs of their ceRNA effect. In this paper, we found the ceRNA effect of C/EBPα and FOXO1 mediated their protein complex formation, furthermore regulated its transcriptional role for AdipoQ , thereby influencing pre-adipocytes adipogenesis . More importantly, we demonstrated that the miR-144 was the decisive factor that mediated the ceRNA effect of C/EBPα and FOXO1 to influence AdipoQ , thus regulated pre-adipocytes adipogenesis. This research will provide a new supplementary idea of the miRNA role in mediating coding RNA interaction that regulates pre-adipocyte adipogenesis.
研究领域:
分子生物学
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细胞生物学
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基因组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF FOOD BIOCHEMISTRY
·
2026
·Vol. 2026
·期 1
·3245873
·
IF 2.3
Caijuan Si,Long Shu,Wenjing Cao,Yuliang Feng,Hui Dong,Xingzhen He,Jingjing Yuan,Songtao Li,Feiwei Cao,Qin Zhu,Peifen Zheng
Andrographolide (Andro) is a major bioactive component of Andrographis paniculata, a medicinal and edible plant with anti-inflammatory effects. However, its effects against ulcerative colitis (UC) and circRNA-related mechanism(s) remain unclear. We established the UC mice model by administrating dextran sulfate sodium (DSS) for 14 days. Treatment with Andro for the last 7 days markedly reversed the shortened colon length, decreased the DAI, and abnormal expression of genes related to inflammation and barriers. Besides, sequencing and qRT-PCR revealed circAsxl2 was upregulated in the DSS group while downregulated after Andro treatment. Moreover, knockdown of circAsxl2 corrected gene expression related to inflammation and barriers in lipopolysaccharide-induced HT-29 cells. Then, miRNA and DEmRNAs associated with circAsxl2 were predicted and used to construct a competitive endogenous RNA (ceRNA) network, in which DEmRNAs mRNA was enriched in immune-related pathways by KEGG. Therefore, Andro possesses the potential to serve as a functional food ingredient for the prevention and management of UC.
✓ 已验证
产品关联
DOI
高影响因子
TOXICOLOGY LETTERS
·
2025
·
IF 2.9
Zhongming Ye,Qihao Huang,Haipeng Wu,Shimei Wang,Boxin Li,Minjuan Zeng,Tikeng Jiang,Biyan Ye,Yixian Wei,Lei Sun,Shaoying Wang,Yutao Zeng,Yuting Chen,Huanwen Tang
Benzene, a recognized carcinogen, is utilized in synthesizing various chemicals. Epidemiological studies have established a positive correlation between benzene exposure and increased incidences of abnormal menstruation and dysmenorrhea. This exposure might also pose risks to the fetal hematopoietic system. However, the precise molecular mechanisms underlying these effects are not fully understood. In this study, a chronic benzene exposure model was established through dynamic inhalation. We assessed the autophagy levels in mouse ovarian granulosa cells and human ovarian granulosa cells treated with 1,4-benzoquinone using molecular biology techniques such as qPCR, Western blot, and transmission electron microscopy (TEM), etc. The experimental results show that Benzene-exposed mice exhibited autophagy, a reduced number of ovarian granulosa cells, and vacuolar lesions in the fallopian tubes. Cell-based experiments demonstrated that benzene exposure significantly upregulated SNHG15 expression in human ovarian granulosa cells ( P < 0.05). The upregulation of SNHG15 enhanced FOXO3 expression via the miR-3143/FOXO3 axis, which in turn increased the transcription of autophagy-related proteins such as Atg5 ( P < 0.05), ultimately leading to excessive autophagy in granulosa cells and ovarian dysfunction. Benzene and its metabolite benzoquinone increase autophagy in ovarian granulosa cells. The lncRNA SNHG15 regulates this autophagy induced by benzene exposure through sponge-like binding to miR-3143/FOXO3, thus impairing ovarian function. Inhibiting SNHG15, miR-3143, and FOXO3 expression markedly reduced autophagy in granulosa cells and ameliorated ovarian dysfunction resulting from benzene exposure. These results suggest that the ceRNA axis involving SNHG15 may be a potential clinical therapeutic target.
研究领域:
毒理学
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分子生物学
·
遗传学
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生殖生物学
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环境卫生
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CELL CYCLE
·
2021
·
IF 4.534
Wei Huang,Feizhou Huang,Rui Zhang,Hongwu Luo
Liver fibrosis is a common response to chronic liver injury, ultimately leading to cirrhosis. The activation of hepatic stellate cells (HSCs) plays a dominant role in liver fibrosis. The regulatory roles of long noncoding RNAs (lncRNAs) in multiple human diseases have been observed. This study was dedicated to investigating the regulatory effects of the lncRNA nuclear paraspeckle assembly transcript 1 (Neat1) on liver fibrosis and HSC activation. Upregulation of Neat1 and cytohesin 3 (Cyth3) and downregulation of miR-148a-3p and miR-22-3p were observed in mouse fibrotic liver tissues. Knockdown of Neat1 or Cyth3 attenuated liver fibrosis and collagen deposition in vivo and the activation of HSCs in vitro. An miR-148a-3p and miR-22-3p inhibitor facilitated HSC activation and collagen fiber expression. Neat1 directly targeted miR-148a-3p and miR-22-3p to modulate Cyth3 expression. Knockdown of Neat1 inhibited Cyth3 expression via the competing endogenous RNA (ceRNA) mechanism of sponging miR-148a-3p and miR-22-3p to regulate liver fibrosis and HSC activation. The ceRNA regulatory network may promote a better understanding of liver fibrogenesis, contribute to an original agreement of liver fibrosis etiopathogenesis and provide insights into the development of a novel domain of lncRNA-directed therapy against liver fibrosis.
研究领域:
分子生物学
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基因组学
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肝病学
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病理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BMC GASTROENTEROLOGY
·
2024
·Vol. 24
·期 1
·1-10
·
IF 2.5
Wen Yuefei,Li Chenyang,Huang Peng,Liu Zhigang,He Yanjun,Liu Bin
Ulcerative colitis (UC) is a chronic inflammatory disease that targets the colon and has seen an increasing prevalence worldwide. In our pursuit of new diagnostic and therapeutic approaches for UC, we undertook a sequencing of colons from UC mouse models. We focused on analyzing their differentially expressed genes (DEGs), enriching pathways, and constructing protein-protein interaction (PPI) and Competing Endogenous RNA (ceRNA) networks. Our analysis highlighted novel DEGs such as Tppp3, Saa3, Cemip, Pappa, and Nr1d1. These DEGs predominantly play roles in pathways like cytokine-mediated signaling, extracellular matrix organization, extracellular structure organization, and external encapsulating structure organization. This suggests that the UC pathogenesis is intricately linked to the interactions between immune and non-immune cells with the extracellular matrix (ECM). To corroborate our findings, we also verified certain DEGs through quantitative real-time PCR. Within the PPI network, nodes like Stat3, Il1b, Mmp3, and Lgals3 emerged as significant and were identified to be involved in the crucial cytokine-mediated signaling pathway, which is central to inflammation. Our ceRNA network analysis further brought to light the role of the Smad7 Long non-coding RNA (lncRNA). Key MicroRNA (miRNAs) in the ceRNA network were pinpointed as mmu-miR-17-5p, mmu-miR-93-5p, mmu-miR-20b-5p, mmu-miR-16-5p, and mmu-miR-106a-5p, while central mRNAs included Egln3, Plagl2, Sema7a, Arrdc3, and Stat3. These insights imply that ceRNA networks are influential in UC progression and could provide further clarity on its pathogenesis. In conclusion, this research deepens our understanding of UC pathogenesis and paves the way for potential new diagnostic and therapeutic methods. Nevertheless, to solidify our findings, additional experiments are essential to confirm the roles and molecular interplay of the identified DEGs in UC.
研究领域:
免疫学
·
分子生物学
·
基因组学
✓ 已验证
DOI
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2020
·
IF 4.872
Yuhao Wu,Junke Wang,Tianxin Zhao,Yuexin Wei,Lindong Han,Lianju Shen,Chunlan Long,Shengde Wu,Guanghui Wei
Di-(2-ethylhexyl) phthalate (DEHP), one of the most commonly used endocrine-disrupting chemicals, has been shown to cause reproductive dysfunction in humans and animal models. However, very few studies have investigated the impact of DEHP at the post-transcriptional level in mouse testes, and the underlying mechanisms remain unclear. In the present research, TM3 Leydig cells were treated with 200 µM phthalic acid mono-2-ethylhexyl ester (MEHP, bio-metabolite of DEHP), and then the mRNA and lncRNA sequencing of TM3 Leydig cells was performed. Mice were exposed prepubertally to 0 or 500 mg DEHP/kg/day. RNA sequencing of mouse testes was performed to verify the RNA-seq results in vitro . The expression patterns of relevant genes and proteins were verified using real-time quantitative polymerase chain reaction (RT-qPCR) and western blotting. DEHP and MEHP exposure led to testicular damage and accelerated cell aging via ROS accumulation. RNA sequencing analyses indicated that FOXO signaling and longevity regulation pathways were activated in resistance to ROS accumulation. FOXO signaling and longevity regulation pathway-related genes and proteins were also activated. By constructing a competing endogenous RNA (ceRNA) network, we observed that the ceRNA network might play a role in regulating FOXO signaling and longevity regulation pathways in response to excessive ROS accumulation and cell aging. In summary, our data here suggests that the ceRNA network may play a role in regulating FOXO signaling and longevity pathways in response to DEHP exposure in mouse testes.
研究领域:
生殖生物学
·
毒理学
·
分子生物学
·
基因组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）