Frontiers in Oncology
·
2021
·
IF 6.244
Yang Jianru,Jia Yang,Wang Bing,Yang Shengrong,Du Kun,Luo Yujie,Li Yunhe,Zhu Bing
Background: The effects of up-regulated CircCHST15 on lung cancer remained unclear. In this study, the role of CircCHST15 in lung cancer was investigated.Methods: Dual-luciferase reporter verified the bioinformatics prediction that CircCHST15 targeted miR-155-5p and miR-194-5p. The correlation between CircCHST15 and PD-L1 was analyzed by Pearson analysis. CCK-8 and colony formation was performed to determine the viability and proliferation of lung cancer cells. After the lung cancer (subcutaneous-xenotransplant) model was established in mice, the T cell subtype and related cytokines in mouse tumor tissues were detected by flow cytometry and ELISA. Moreover, the expressions of CircCHST15, miR-155-5p, miR-194-5p, immune-related, and proliferation-related factors of the lung cancer cells or mice tumor tissues were detected by immunohistochemistry, RT-qPCR, or Western blot.Results: CircCHST15 and PD-L1 were high-expressed in lung cancer, and the two was positively correlated. CircCHST15 targeted miR-155-5p and miR-194-5p, the later further targeted PD-L1. Lung cancer cell viability and proliferation were increased by miR-155-5p and inhibited by miR-194-5p. CircCHST15 located in the cytoplasm promoted tumor growth, down-regulated the expressions of miR-155-5p and miR-194-5p, and up-regulated the expressions of PD-L1, Ki-67, PCNA, CCL17, CCL22, IFN-γ, TNF-β, and IL-10. Also, CircCHST15 decreased the CD8+ cells in mouse blood and tumor, but increased the Tregs in mouse tumor. PD-L1 inhibitor showed an opposite effect to CircCHST15 on mouse tumors.Conclusion: CircCHST15 sponged miR-155-5p and miR-194-5p to promote the PD-L1-mediated immune escape of lung cancer cells.
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EXPERIMENTAL ANIMALS
·
2020
·
IF 1.574
Yongxia Cheng,Jingchao Li,Chong Wang,Heran Yang,Ying Wang,Tao Zhan,Sufen Guo,Jun Liang,Yuxin Bai,Jianbo Yu,Guibo Liu
Diabetic cardiomyopathy (DCM) is one of the cardiovascular complications of diabetes mellitus independent of hypertension, coronary disease, and other heart diseases. The development of DCM is multifactorial and hard to detect at an early stage. Long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (Malat1) is emerging as a regulator of DCM, the underlying mechanism of its role in DCM has not been elaborated yet. In this study, we established a mouse DCM model via streptozocin injection as evidenced by cell hypertrophy and cell apoptosis of myocardial tissue, and found that Malat1 expression was upregulated in the myocardium in DCM mice. Meanwhile, elevated expression of pro-apoptotic factors p53, p21, cleaved caspase 3, cleaved caspase 9 and BAX, and down-regulation of anti-apoptotic BCL-2 were observed in DCM myocardium. We further investigated the effect of Malat1 on cardiomyocytes under high glucose condition by silencing Malat1 with its specific short-hairpin RNA. Like in vivo, expression of Malat1 in cardiomyocytes was notably raised, remarkable cell apoptosis and changes in apoptosis-related factors were also observed following high glucose treatment. Besides, we validated that Malat1 acted as a sponge of miR-181a-5p. Inhibition of miR-181a-5p could, at least partially, abolish Malat1 knockdown-induced alteration in cardiomyocytes. In addition, p53, a critical regulator of apoptosis, was validated to be a downstream target of miR-181a-5p. In summary, our findings reveal that Malat1 knockdown attenuates high glucose-induced cardiomyocyte apoptosis via releasing miR-181a-5p, and this mechanism may provide us with new diagnosis target of DCM.
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ENVIRONMENTAL POLLUTION
·
2020
·
IF 6.793
Tian-Xin Zhao,Jun-Ke Wang,Lian-Ju Shen,Chun-Lan Long,Bin Liu,Yi Wei,Lin-Dong Han,Yue-Xin Wei,Sheng-De Wu,Guang-Hui Wei
Di-(2-ethylhexyl) phthalate (DEHP) is a common environmental endocrine disrupting chemical that may induce male reproductive disorders. Exposure to DEHP at a prepubertal stage could lead to prepubertal testicular injury, but the underlying mechanisms remain unclear. In this study, we exposed Sprague-Dawley rats to 0, 250, and 500 mg DEHP per kg body weight per day at the prepuberty stage from postnatal day 22 (PND 22) to PND 35 by oral gavage. Testicular injury and oxidative stress were evaluated, and the levels of 6-methyladenosine (m6A) modification and expression of modulator genes for RNA methylation were measured in testes . Furthermore, m6A modification of the important antioxidant transcription factor Nrf2 was analyzed using methylated RNA immunoprecipitation qPCR. Our results show that DEHP worsened testicular histology, decreased testosterone concentrations, downregulated expression of spermatogenesis inducers, enhanced oxidative stress, inhibited the Nrf2-mediated antioxidant pathway, and increased apoptosis in testes. Additionally, DEHP increased global levels of m6A RNA modification and altered the expression of two important RNA methylation modulator genes, FTO and YTHDC2 . Moreover, m6A modification of Nrf2 mRNA increased upon DEHP exposure. Overall, these findings link oxidative stress imbalance with epigenetic effects of DEHP toxicity and provide insight into the testicular toxicity of DEHP from the new perspective of m6A modification.
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NEW JOURNAL OF CHEMISTRY
·
2018
·Vol. 42
·期 17
·14325-14331
·
IF 3.201
Ruiqing Feng,Longlong Li,Bing Li,Jinhui Li,Dan Peng,Yitao Yu,Qiuhong Mu,Ning Zhao,Xiaoqiang Yu,Zhenhua Wang
We have synthesized a two-photon organic small-molecule probe (DMI), which has a considerable two-photon absorption cross section (δ) value and selectively stained endogenous RNA in the nucleolus and the cytoplasm of living cells with outstanding membrane permeability. The titrations, fluorescence imaging and RNase digest test indicate markedly higher affinity for endogenous RNA. The double assay of DMI and SYTOX Blue nucleic acid stain (S-11348) showed that the probe possesses excellent membrane permeability to living cells, and a co-staining experiment with the classic DNA-staining dye DAPI indicated that it has excellent counterstain compatibility. Moreover, DMI exhibited good photostability when continuously illuminated by constant femtosecond pulses. These results demonstrate that DMI is an attractive two-photon fluorescent probe for visualizing RNA in living cells.
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INSECT BIOCHEMISTRY AND MOLECULAR BIOLOGY
·
2025
·
IF 3.7
Fuqiang Rao,Jie Yang,Danhao Peng,Xinghao Li,Zhaoqun Li,Deguang Liu
Herbivorous insects rely on olfactory cues to select oviposition sites on host plants, which is a process critical for their reproductive success. The rape stem weevil, Ceutorhynchus asper Roel. (Coleoptera: Curculionidae), is a major pest that causes significant damage to rapeseed and other cruciferous crop production, yet the chemical and molecular mechanisms underlying its oviposition preference remain unknown. Our behavioral assays revealed that C. asper females strongly avoided pre-infested rapeseed plants. Five monoterpenes (p-cymene, 1,8-cineole, ocimene, camphor, and α-pinene) were identified as herbivore-induced plant volatiles of C. asper -infested plants, with their emission levels significantly higher than those in healthy plants. Among these five compounds, subsequent electroantennogram (EAG) screening revealed that only 1,8-cineole triggered significant responses in C. asper and showed a concentration-dependent sensitivity. Behavioral assays showed that female C. asper exhibited significant behavioral and oviposition avoidance when exposed to 1,8-cineole. We identified CaspOR39 as the specific odorant receptor for 1,8-cineole, with molecular docking for prediction of the binding affinity and key residues. RNAi of CaspOR39 abolished female EAG responses, as well as behavioral and oviposition avoidance of 1,8-cineole. These results revealed a sex-specific chemical sensing mechanism: female C. asper can utilize CaspOR39 to detect 1,8-cineole as a key cue of plant infestation, driving adaptive oviposition behaviors of this beetle. Our results provide mechanistic and molecular insights into CaspOR39-mediated oviposition behaviors of C. asper , and a basis for the development of semiochemical-based strategies for management of this weevil.
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CELL DEATH AND DIFFERENTIATION
·
2024
·
IF 13.7
Cai Jiangxue,Li Chenxuan,Liu Suyuan,Tan Meiling,Sun Yiran,Sun Xiaoxiao,Yang Miaoxin,He Bin
The cellular stress response system in immune cells plays a crucial role in regulating the development of inflammatory diseases. In response to cellular damage or microbial infection, the assembly of the NLRP3 inflammasome induces pyroptosis and the release of inflammatory cytokines. Meanwhile, Angiogenin (Ang)-mediated transfer RNA-derived small RNAs (tsRNAs) promote cell survival under stressful conditions. While both tsRNAs and inflammasomes are induced under stress conditions, the interplay between these two systems and their implications in regulating inflammatory diseases remains poorly understood. In this study, it was demonstrated that Ang deficiency exacerbated sodium arsenite-induced activation of NLRP3 inflammasome and pyroptosis. Moreover, Ang-induced 5′-tsRNAs inhibited NLRP3 inflammasome activation and pyroptosis. Mechanistically, 5′-tsRNAs recruit DDX3X protein into stress granules (SGs), consequently inhibiting the interaction between DDX3X and NLRP3, thus leading to the suppression of NLRP3 inflammasome activation. Furthermore, in vivo results showed that Ang deficiency led to the downregulation of tsRNAs, ultimately leading to an exacerbation of NLRP3 inflammasome-dependent inflammation, including lipopolysaccharide-induced systemic inflammation and type-2 diabetes-related inflammation. Altogether, our study sheds a new light on the role of Ang-induced 5′-tsRNAs in regulating NLRP3 inflammasome activation via SGs, and highlights tsRNAs as a promising target for the treatment of NLRP3 inflammasome-related diseases.
研究领域:
免疫学
·
分子生物学
·
炎症
·
代谢紊乱
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PLANT CELL AND ENVIRONMENT
·
2024
·
IF 6
Linlin Su,Wenyun Li,Xiaohua Chen,Pengcheng Wang,Diqiu Liu
The root rot mainly caused by Fusarium solani is a bottleneck in the cultivation of Panax notoginseng . In this study, we reported a gene encoding a plant cell wall structural protein, P. notoginseng proline-rich protein (PnPRPL1), whose transcription was upregulated by F. solani and induced by some hormone signals. The PnPRPL1 recombinant protein significantly inhibited the growth and conidial germination of the root rot pathogens. Downregulation of PnPRPL1 by RNA interference (RNAi) in P. notoginseng leaves increased the susceptibility to F. solani , whereas overexpression of PnPRPL1 in tobacco ( Nicotiana tabacum ) enhanced the resistance to F. solani . Compared with wild-type tobacco, the PnPRPL1 -overexpressing transgenic tobacco had higher reactive oxygen species (ROS)-scavenging enzyme activities, lower ROS levels, and more lignin and callose deposition. The opposite results were obtained for the P. notoginseng expressing PnPRPL1 RNAi fragments. Furthermore, the PnPRPL1 promoter transcription activity was induced by several plant hormones and multiple stress stimuli. In addition, the transcription factor PnWRKY27 activated the expression of PnPRPL1 by directly binding to the promoter region. Thus, PnPRPL1 , which is positively regulated by a WRKY transcription factor, encodes an antimicrobial protein that also mediates ROS homoeostasis and callose/lignin deposition during the response to F. solani infection.
研究领域:
植物病理学
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分子生物学
·
植物遗传学
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TALANTA
·
2025
·
IF 6.1
Jingbo Sun,Liushunhao Chen,Hongchen Li,Chen Xu,Dong Xu,Jiali Ren
Biological staining is essential for imaging, functional investigation, and disease diagnostics. In this research, innovative green-emissive carbon dots (G-CDs) were hydrothermally prepared from 1,2,4-triaminobenzene and ascorbic acid (AA) and further explored for versatile imaging of mammalian cells, plant cells, and microorganisms. The G-CDs, exhibiting fluorescence enhancement, outperform conventional dyes in terms of staining efficiency and specificity across various biological systems. For mammalian cells (SH-SY5Y, Hep3B, and HEK293), the G-CDs can stain both the nuclei and nucleoli in 10 min via a micropinocytic endocytosis approach, with the latter brighter. Fluorescence enhancement was greater for RNA than for DNA. Interestingly, for plant cells, only cell walls were stained, because positive charges on G-CDs enable strong adsorption onto the negatively charged cell walls, thereby hindering their further entry. G-CDs can stain cell walls and nuclei for fungi (including Aspergillus flavus and Aspergillus niger ), and cell walls and nucleoids for bacteria ( Bacillus subtilis and Escherichia coli ). The targeted staining arises from both the binding of G-CDs to DNA, RNA, pectin, peptidoglycan, and cellulose, and fluorescence enhancement due to surface passivation inhibiting rotation and vibration of functional groups. Electrostatic interactions, coordination, hydrogen bonding, and amidation collectively account for the interactions between G-CDs and these biomolecules . Finally, their practical applications in leucorrhea examinations demonstrated their capability to differentiate between bacterial and fungal vaginosis, highlighting their potential in clinical diagnostics.
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INTERNATIONAL IMMUNOPHARMACOLOGY
·
2025
·
IF 4.7
Shuangping Ma,Xianting Liu,Yiran Qin,Yilong Wang,Yu Feng,Binfeng Cheng,Lei Wang
Sickle cell disease (SCD) and β-thalassemia are autosomal recessive genetic disorders caused by abnormal synthesis of β-globin chains. Reversing the transition of fetal-to-adult hemoglobin after birth shows great potential in the treatment of these disorders. Here, we identified an RNA-binding protein, RBM3, as a novel HbF (HbF, α 2 γ 2 ) suppressor. Specifically, downregulation of RBM3 in the erythroid progenitor cell line HUDEP-2 robustly induced γ-globin expression at both the mRNA and protein levels, with a slight impact on β-globin levels. Conversely, overexpression of RBM3 in HUDEP-2 cells led to a marked reduction in γ-globin expression. According to the previous study, we introduced specific inhibitors targeting FAK and Src to block RBM3 protein synthesis. Surprisingly, treatment with the FAK inhibitor resulted in a significant increase in γ-globin expression, whereas the Src inhibitor had little effect. Mechanistically, RBM3 depletion accelerated the degradation of BCL11A protein at the post-transcriptional level, without affecting its mRNA stability. Moreover, RBM3 silencing restricted the overall translation efficiency while selectively lifting the ratio of γ-globin mRNA in polysomes. Importantly, downregulation of RBM3 did not impair erythropoiesis progression, suggesting a safe and effective therapeutic strategy for SCD and β-thalassemia. Our findings identify RBM3 as a negative regulator of HbF expression and reveal it as a novel molecular target for modulating the fetal-to-adult hemoglobin switch, holding great promise for the treatment of SCD and β-thalassemia.
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CELL PROLIFERATION
·
2023
·
IF 8.5
Yun Lv,Ziyan Rao,Lulu Liu,Jun Jia,Chenyang Wu,Jun Xu,Yuanyuan Du,Yinan Liu,Bei Liu,Jihang Shi,Guangya Li,Dongyu Zhao,Hongkui Deng
Derivation of human hepatocytes from pluripotent stem cells in vitro has important applications including cell therapy and drug discovery. However, the differentiation of pluripotent stem cells into hepatocytes in vitro was not well recapitulated the development of liver. Here, we developed a differentiation protocol by mimicking the two-stage development of hepatoblasts, which permits the efficient generation of hepatic progenitor cells from chemically induced pluripotent stem cells (hCiPSCs). Single-cell RNA sequencing (scRNA-seq) indicates the similarity between hepatoblasts differentiated in vitro and in vivo. Moreover, hCiPSC-derived hepatic progenitor cells can further differentiate into hepatocytes that are similar to primary human hepatocytes with respect to gene expression and key hepatic functions. Our results demonstrate the feasibility of generating hepatic progenitor cells and hepatocytes from hCiPSCs with high efficiency and set the foundation for broad translational applications of hCiPSC-derived hepatocytes.
研究领域:
干细胞研究
·
分子生物学
·
再生医学
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ANALYTICAL CHEMISTRY
·
2022
·
IF 8.008
Fang Yang,Shunmei Li,Xia Li,Ruo Yuan,Yun Xiang
Accurate and specific imaging of low-abundance intracellular microRNAs (miRNAs) is crucial for monitoring cellular processes and disease diagnosis. Despite the fact that nucleic acid amplification technologies have shown great advantages for the detection of trace targets, their live cell imaging applications remain a major challenge because of the insufficient stability and slow reaction kinetics of the probes in cellular delivery and imaging. Herein, we demonstrate the synthesis of DNA-cross-linked polymeric lighting-up nanogels (DPLNs) through the DNA hairpin-based hybridization chain reaction within nanoscale-confined space for monitoring and imaging live cell miRNA-21 with high sensitivity. Cascaded catalytic hairpin assembly of two hairpin signal probes confined in the DPLNs can be triggered by the target miRNA, causing substantially amplified fluorescence resonance energy transfer signals with accelerated reaction kinetics. Moreover, the DPLNs show low cytotoxicity and highly enhanced nuclease resistance and can be successfully delivered into live cells for imaging low levels of miRNA-21. In addition, the DPLN probes can be readily tuned by specific sequences for monitoring various molecular targets in live cells for important biological and biomedical applications.
研究领域:
生物化学
·
分子生物学
·
医学诊断
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高影响因子
ARCHIVES OF DERMATOLOGICAL RESEARCH
·
2024
·Vol. 317
·期 1
·1-12
·
IF 1.8
Mu Yanan,Lian Chen,Chen Xinghui,Yang Xueying,Li Dongxia,Zhang Yi
Tumor-derived exosomes that transport MicroRNAs significantly influence cutaneous squamous cell carcinoma(CSCC) progression. However, the molecular mechanisms of exosomal MicroRNA-31 regulation of CSCC are mostly undefined. To determine whether a targeting relationship exists between MicroRNA-31 (miR-31) in CSCC-derived exosomes and the tumor suppressor RhoBTB1, and the regulatory effect of the relationship on tumor cells. Immunoblotting and quantitative PCR were used to measure miR-31 and RhoBTB1 levels in various cells and exosomes. Differential ultracentrifugation was used to isolate exosomes. MTT and Transwell assays were used to assess cell proliferation, migration, and invasion. Dual luciferase reporter assays were used to assess the direct interaction between miR-31 and the tumor suppressor RhoBTB1 in cutaneous squamous cell carcinoma (CSCC)-derived exosomes. Compared with a human skin keratinocyte cell line, in CSCC cell lines RhoBTB1 was downregulated and miR-31 levels were elevated. Exosomal miR-31 from CSCC cell lines directly targeted RhoBTB1 by binding to the 3’ UTR of RhoBTB1. This interaction suppressed expression of RhoBTB1 and enhanced CSCC cell proliferation, migration, and invasion. MicroRNA-31 in CSCC-derived exosomes can enhance CSCC cell proliferation, migration, and invasion by suppressing expression of RhoBTB1. This finding explains, in part, the molecular mechanism of CSCC. Investigative approaches focused on suppressing miR-31 or enhancing RhoBTB1 signaling pathways are promising avenues for developing targeted therapies for CSCC.
研究领域:
肿瘤学
·
分子生物学
·
细胞生物学
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