Translational Oncology
·
2021
·
IF 4.243
Qiuli Wang,Dong Liang,Peng Shen,Yang Yu,Yuan Yan,Wei You
Previous study has confirmed that hsa_circ_0092276 is highly expressed in doxorubicin (DOX)-resistant breast cancer cells, indicating that hsa_circ_0092276 may be involved in regulating the chemotherapy resistance of breast cancer. Here we attempted to investigate the biological role of hsa_circ_0092276 in breast cancer. We first constructed DOX-resistant breast cancer cells (MCF-7/DOX and MDA-MB-468/DOX). The 50% inhibiting concentration of MCF-7/DOX and MDA-MB-468/DOX cells was significantly higher than that of their parental breast cancer cells, MCF-7 and MDA-MB-46. MCF-7/DOX and MDA-MB-468/DOX cells also exhibited an up-regulation of drug resistance-related protein MDR1. Compared with MCF-7 and MDA-MB-46 cells, hsa_circ_0092276 was highly expressed in MCF-7/DOX and MDA-MB-468/DOX cells. Hsa_circ_0092276 overexpression enhanced proliferation and the expression of LC3-II/LC3-I and Beclin-1, and repressed apoptosis of breast cancer cells. The effect of hsa_circ_0092276 up-regulation on breast cancer cells was abolished by 3-methyladenine (autophagy inhibitor). Hsa_circ_0092276 modulated autophagy-related gene 7 (ATG7) expression via sponging miR-384. Hsa_circ_0092276 up-regulation promoted autophagy and proliferation, and repressed apoptosis of breast cancer cells, which was abolished by miR-384 overexpression or ATG7 knockdown. In addition, LV-circ_0092276 transfected MCF-7 cell transplantation promoted autophagy and tumor growth of breast cancer in mice. In conclusion, our data demonstrate that hsa_circ_0092276 promotes autophagy and DOX resistance in breast cancer by regulating miR-348/ATG7 axis. Thus, this article highlights a novel competing endogenous RNA circuitry involved in DOX resistance in breast cancer.
研究领域:
肿瘤学
·
分子生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Open Medicine
·
2022
·Vol. 17
·期 1
·1821-1832
·
IF 2.123
Changsheng Wang,Rongsheng Chen,Xitian Zhu,Xiaobo Zhang
This study aimed to explore the effects of long non-coding RNAs LINC00689 (LINC00689) in human nucleus pulposus cells (NPCs). NPCs were isolated and their morphology was observed. The proliferation and apoptosis of NPCs, and the levels of LINC00689, miR-3127-5p, Bax, Bcl-2, Cleaved caspase-3, ATG5, ATG7, p62, and LC3Ⅱ/LC3I were detected. Interrelations of LINC00689, miR-3127-5p, and ATG7 were analyzed. LINC00689 was down-regulated yet miR-3127-5p was up-regulated in NPCs. LINC00689 could competitively bind with miR-3127-5p, and ATG7 was targeted by miR-3127-5p in NPCs. Overexpressed LINC00689 promoted proliferation yet inhibited apoptosis of NPCs, whereas LINC00689 silencing did the opposite. Overexpressed LINC00689 raised ATG7 level and LC3Ⅱ/LC3I value yet reduced that of p62 level, but the depletion of LINC00689 did the contrary. ATG7 silencing abolished the effects of overexpressed LINC00689 in NPCs, and likewise, up-regulation of miR-3127-5p overturned the effects of overexpressed LINC00689 in NPCs. Collectively, the up-regulation of LINC00689 inhibits the apoptosis of NPCs via miR-3127-5p/ATG7 axis-mediated autophagy.
研究领域:
分子生物学
·
细胞生物学
·
基因组学
✓ 已验证
DOI
PubMed
高影响因子
Materials Today Bio
·
2025
·
IF 10.2
Qiumei Lan,Mengtian Fan,Fengmei Zhang,Qian Gong,Jiayan Zhong,Miao Yi,Qiqi Zeng,Jianqiang Chen,Yiming Pan,Nana Geng,Biao Kuang,Yu Du,Chuanrong Zhao,Deping Zeng,Chunliang Zhao,Zhen Li,Guixue Wang,Fengjin Guo
Bone regeneration remains a formidable challenging due to impaired energy metabolism and the limited osteogenic potential of transplanted stem cells. Mitochondrial homeostasis orchestrates osteogenesis, with mitophagy maintaining the metabolic rhythm essential for bone formation. However, the role of autophagy related gene 7(ATG7), a pivotal regulator of mitochondrial function, in bone regeneration remains elusive. In this study, we developed a ATG7-overexpressing bone marrow mesenchymal stem cells (ATG7-BMSCs) encapsulated within a thermoresponsive chitosan (CS) hydrogel, creating a biocompatible, living platform capable of adapting to physiological conditions. The hydrogel exhibited excellent injectability, physiological gelation at 37 °C, and prolonged biocompatibility, providing a favorable microenvironment for stem cell survival and proliferation. The system was evaluated through in vitro assays for mitochondrial function and osteogenic differentiation, as well as in vivo using rat cranial and femoral defect models. Mechanistically, ATG7 activation enhanced mitophagy, preserved mitochondrial integrity, reduced reactive oxygen species (ROS) accumulation, and reactivated oxidative phosphorylation via the PI3K-AKT signaling pathway, thereby reprogramming osteogenic metabolism and promoting differentiation. Conversely, ATG7 deficiency led to mitochondrial dysfunction, glycolytic dependence, and impaired bone formation. In vivo, the ATG7-BMSC@CS hydrogel markedly accelerated new bone formation and mineral density recovery while maintaining excellent injectability, biocompatibility, and systemic safety. Collectively, this study identifies ATG7-driven mitophagy as a critical regulator of osteogenic metabolism and bone formation, and establishes a smart, living hydrogel platform that seamlessly integrates metabolic reprogramming with stem cell delivery. This strategy provides a conceptual blueprint for next-generation, metabolism-oriented bone repair at the intersection of cell biology, biomaterials, and precision medicine.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Clinical Interventions in Aging
·
2022
·
IF 3.829
Bao Hai,Yunlong Ma,Xiaoyu Pan,Lei Yong,Chen Liang,Guanping He,Chenlong Yang,Bin Zhu,Xiaoguang Liu
Background Disc degeneration (DD) is one of the common diseases worldwide, which deeply influences normal life and leads to excruciating pain. However, an effective treatment for DD is still not identified.Method The present study systemically examined the effect of melatonin on annulus fibrosus (AF) cells of patients with DD.Results Melatonin had the effect of promoting proliferation, inducing autophagy, and suppressing apoptosis on AF cells of patients with DD. Moreover, melatonin contributed to the translation and transcription of autophagy-related protein ATG7 and inhibited the function of miR-106a-5p in AF cells. In addition, the results suggested that miR-106a-5p mediated the expression of ATG7 by directly binding to its 3′UTR in AF cells.Conclusion This research not only gained a deep insight of melatonin mode of action, but also indicated its potential target signaling pathway in AF cells.
研究领域:
神经病学
·
细胞生物学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Microbiology Spectrum
·
2023
·Vol. 11
·期 3
·
IF 3.7
Jinchao Xing,Chen Hu,Siqi Che,Yixin Lan,Lihong Huang,Lele Liu,Youqin Yin,Huanan Li,Ming Liao,Wenbao Qi
Japanese encephalitis virus (JEV) is a typical mosquito-borne flavivirus that can cause central nervous system diseases in humans and animals. Host factors attempt to limit virus replication when the viruses invade the host by using various strategies for replication. It is essential to clarify the host factors that affect the life cycle of JEV and explore its underlying mechanism. Here, we found that USP1-associated factor 1 (UAF1; also known as WD repeat-containing protein 48) modulated JEV replication. We found that JEV propagation significantly increased in UAF1-depleted Huh7 cells. Moreover, we found that knockdown of UAF1 activated cell autophagic flux in further functional analysis. Subsequently, we demonstrated that autophagy can be induced by JEV, which promotes viral replication by inhibiting interferon-stimulated gene (ISG) expression in Huh7 cells. The knockdown of UAF1 reduced ISG expression during JEV infection. To explore the possible roles of autophagy in UAF1-mediated inhibition of JEV propagation, we knocked out ATG7 to generate autophagy-deficient cells and found that depletion of UAF1 failed to promote JEV replication in ATG7 knockout cells. Moreover, in ATG7-deficient Huh7 cells, interference with UAF1 expression did not lead to the induction of autophagy. Taken together, these findings indicate that UAF1 is a critical regulator of autophagy and reveal a mechanism by which UAF1 knockdown activates autophagy to promote JEV replication.IMPORTANCE Host factors play an essential role in virus replication and pathogenesis. Although UAF1 is well known to form complexes with ubiquitin-specific proteases, little is known about the function of the UAF1 protein itself. In this study, we confirmed that UAF1 is involved in JEV replication. Notably, we discovered a novel function for UAF1 in regulating autophagy. Furthermore, we demonstrated that UAF1 modulated JEV replication through its autophagy regulation. This study is the first description of the novel function of UAF1 in regulating autophagy, and it clarifies the underlying mechanism of the antiviral effect of UAF1 against JEV. These results provide a new mechanistic insight into the functional annotation of UAF1 and provide a potential target for increasing virus production during vaccine production.
研究领域:
病毒学
·
分子生物学
·
细胞生物学
·
传染病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Microbiology Spectrum
·
2023
·Vol. 11
·期 6
·
IF 3.7
Minyu Wang,Zheng Wang,Duncan James Lessing,Min Guo,Weihua Chu
Fusobacterium nucleatum is a harmful bacterium that produces hydrogen sulfide by metabolizing sulfur-containing amino acids, both of which have been shown to promote/initiate the development of various cancers, such as colorectal cancer, liver cancer, as well as lung cancer. However, few studies have reported how F. nucleatum acts on gut microbiota, influences the autophagy process, and promotes the development of colorectal cancer through the metabolite hydrogen sulfide. It was found that HCT116 cells secreted more inflammatory factors and showed higher survival as well as migration rate when given a pathological concentration of hydrogen sulfide. Using cellular transcriptome sequencing, it could be seen that after giving HCT116 cells F. nucleatum or F. nucleatum with L-cysteine, many inflammation-related signaling pathways, including autophagic pathways, were elevated compared to the control group. In vivo, the mice in the model groups displayed cancer progression, and the expression of some of the autophagy-related genes, DRAM1, NBR1, ATG7, MAP1LC3A were also increased in mice given F. nucleatum or F. nucleatum with L-cysteine when compared to the untreated control mice. The number of certain probiotic bacteria and fungi in the mice given F. nucleatum or F. nucleatum and L-cysteine decreased significantly; in contrast, the number of potentially pathogenic bacteria and fungi increased. These findings suggest that F. nucleatum and its metabolite hydrogen sulfide can modulate intestinal microbiota and autophagy as well as promote the development and progression of colorectal cancer.
研究领域:
微生物学
·
癌症生物学
·
分子生物学
·
胃肠病学
✓ 已验证
DOI
高影响因子
MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS
·
2015
·
IF 2.415
Haibo Mu,Qianjin Liu,Hong Niu,Dongdong Wang,Jiangjiang Tang,Jinyou Duan
Toxic DNA–protein crosslinks (DPCs) can result from exposure to radiation or chemotherapeutic agents. DPCs can also accumulate during aging or stress. However, the cellular mechanisms underlying clearance of DPCs remain largely unknown. Here, we have identified an important role of autophagy in the processing of DPCs induced by three representative agents: formaldehyde, a chemical used widely in industry; UV light; and camptothecin, a cytotoxic anticancer drug. Autophagy inhibitors, 3-methyladenine (3-MA) or chloroquine (CQ), promoted the accumulation of DPCs in damaged cells and injured organs. siRNA-mediated silencing of Atg5 or Atg7, two essential components for the formation of the autophagosome, gave similar results. In contrast, the autophagy inducer rapamycin (RAP) attenuated DPCs in vitro and in vivo . Our findings reveal the importance of autophagy in controlling the level of DPCs, and may open up a new avenue for understanding the formation and clearance of this detrimental DNA adduct.
研究领域:
细胞生物学
·
分子生物学
·
癌症研究
·
衰老研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NUTRITIONAL BIOCHEMISTRY
·
2026
·
IF 5.2
Yan-Ni He,Shi-Ying Li,Pei Xu,Xing-Yue Zhou,Jing Zeng,Da-Lian Qin,Geng Xiong,Lu Yu,Wei Ren,An-Guo Wu,Jian-Ming Wu,Xiao-Gang Zhou
Aging is characterized by progressive cellular dysfunction and increased susceptibility to chronic diseases. Enhancing autophagy, a key cellular clearance process, offers a promising strategy to combat aging. In this study, we investigated the autophagy-inducing and anti-aging properties of Salvia plebeia R. Br. ethanol extract (SPE) using in vitro and in vivo models. Our results showed that SPE enhanced autophagosome and autolysosome formation, elevated LC3-II and Beclin-1 levels, and reduced p62 expression in human foreskin fibroblasts (HFFs), confirming its autophagy-inducing activity. SPE also mitigated D-galactose (D-gal)-induced cellular senescence, reducing SA-β-gal staining, senescence markers (p16, p21), SASP factors, and γ-H2AX foci. These effects were Atg7-dependent, as Atg7 knockout abolished the benefits, highlighting autophagy’s role in SPE’s action. In vivo, SPE improved physical function, reversed cellular senescence, enhanced antioxidant defenses, and restored autophagic activity in D-gal-induced prematurely senescent mice. Furthermore, SPE alleviated age-related cognitive decline, reduced neuronal damage, increased synaptic density, and mitigated Tau accumulation. Notably, SPE demonstrated good tolerability over 12 weeks, with stable body weight, no apparent tissue injury, and unchanged serum ALT, AST, and creatinine. Chemical profiling identified rosmarinic acid (RA) as a major bioactive constituent that recapitulated key autophagy- and senescence-related effects in vitro. These findings suggest that SPE is a promising natural autophagy enhancer with potential to promote healthy aging, combat age-related diseases, and serve as a novel therapeutic strategy for cellular dysfunction in aging.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2019
·Vol. 8
·期 1
·201-211
·
IF 5.251
Shuli Man,Miao Li,Jin Zhou,Haiyue Wang,Jinyan Zhang,Long Ma
Fe3O4 magnetic nanoparticles (MNPs), as one of the most intensively researched NPs, have a range of applications in cancer treatments. In current research, we have focused on the influences of MNPs on cancer cells. We chose polyethyleneimine (PEI) coated MNPs (PEI-MNPs) as a model and they are colloidally stable in biological media. It can be proved that PEI-MNPs result in autophagy induction via mTOR-Akt-p70S6 K and ATG7 signaling pathways. For the first time, we have reported that PEI-MNPs activate both NF-κB and TGF-β signaling, two key pro-inflammatory pathways, in cancer cells. More significantly, we have found that autophagy induction and NF-κB and TGF-β activation can be efficiently suppressed through the inhibition of PEI-MNP dependent reactive oxygen species (ROS) over-production. ROS are deemed as a ‘double edge sword’ for cancer cells, owing to the cancer-suppressing and cancer-promoting actions. Our findings would be useful for designing MNPs induced ROS anti-cancer strategies or diminishing long-term toxic effects.
研究领域:
纳米技术
·
癌症生物学
·
细胞信号传导
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BRAIN RESEARCH BULLETIN
·
2022
·
IF 3.715
Lin Bai,Yingying Wu,Ruike Wang,Rundong Liu,Mengchen Liu,Qiong Li,Yue Ba,Huizhen Zhang,Guoyu Zhou,Fangfang Yu,Hui Huang
As a ubiquitous toxic heavy metal, lead (Pb) exposure is known to be implicated in the onset and development of neurodegenerative diseases which may cause more serious health hazards with age and the accumulation of Pb in the body. Autophagy is the main degradation route for abnormal aggregated proteins and damaged cell organelles. Here, we aimed to study the effects of adolescent Pb exposure on autophagy at different life nodes. In this study, we developed a time-series model of Pb exposure in mice and randomly divided 4-week-old male C57BL/6 mice into six groups (4 C, 13 C, 16 C, 4Pb, 13Pb and 16Pb). Mice in Pb groups was consumed deionized water containing 0.2 % Pb(Ac) 2 for 3 months and then reared to anticipated life nodes, while the control group consumed deionized water. Western blot and Real-time qPCR were used to assess the effects of developmental Pb exposure on individual components of the autophagy machinery and modulation of microtubule-associated protein 1 light chain 3 (LC3) at each age stage. Our results showed that Pb exposure during adolescence reduced the p-mTOR/mTOR ratios with enhanced expression of Beclin-1, Atg12 and Atg7in both the hippocampus (HPC) and prefrontal cortex (PFC) of senescent mice while upregulation of LC3II/LC3I ratios and p62 suggested that autophagy mediates degradation was interrupted. Overall, we confirm that Pb exposure during adolescence promotes autophagic processes in the aged mice brain and that autophagic degradation is hindered, ultimately leading to a failure of autophagic degradation.
研究领域:
毒理学
·
神经科学
·
分子生物学
·
发育生物学
·
衰老研究
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2019
·
IF 4.784
Qiang Chu,Shuang Zhang,Lushuang Yu,Yonglu Li,Yangyang Liu,Xiang Ye,Xiaodong Zheng
The tubers of Apios americana Medikus possess high nutritional value and have been used as food in many countries for a long time. However, few researches have focused on the tuber polysaccharides. In the present study, a purified polysaccharide (ATP-1) was isolated with the average molecular weights of 12.16 kDa. ATP-1 significantly suppressed the release of nitric oxide (NO) and inflammatory cytokines from LPS-induced RAW 264.7 cells, as well as oxidative stress and mitochondrial dysfunction. Meanwhile, ATP-1 reduced oxidative damage via the NF-κB, MAPKs and Nrf2-Keap1 signaling pathways in RAW264.7 macrophages. Furthermore, autophagy was activated by HMGB1-Beclin1, Sirt1-FoxO1 and Akt-mTOR signaling pathways, leading to a relief of oxidative stress, mitochondrial dysfunction, inflammation and an expression enhancement of autophagy-related proteins, such as LC3, Beclin1, Atg4, Atg5, and Atg7. In summary, our results suggested that ATP-1 might help to activate the anti-inflammation system，resulting in prevention of LPS-induced damage in RAW264.7 cells.
研究领域:
药理学
·
免疫学
·
细胞生物学
·
生物化学
✓ 已验证
DOI
PubMed
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
·
2019
·
IF 3.775
Leying Jiang,Zhen Li,Yixi Xie,Liangliang Liu,Yi Cao
Recent studies suggest that phytochemicals , as part of the food matrix, might alter the toxicity of nanoparticles (NPs); however, relatively few studies have investigated the impact of anthocyanidins on the toxicity of NPs to cells lining the gastrointestinal tract. Therefore, this study used cyanidin chloride (CC) as the model for anthocyanidins and investigated the effects of CC on the toxicity of ZnO or Ag NPs to Caco-2 cells. Exposure to ZnO but not Ag NPs significantly induced cytotoxicity. The presence of CC, but not its analog quercetin (Qu), modestly protected Caco-2 cells from ZnO NP exposure. However, the intracellular superoxide, Zn ions , or release of interleukin-8 after ZnO NP exposure were not significantly affected by the presence of CC. Rather, CC promoted the expression of autophagic genes ATG5 , ATG7 , and BECN1 as well as the ratio of LC3-II/I after exposure to ZnO NPs. Meanwhile, the presence of autophagic inhibitors (chloroquine, NH 4 Cl, bafilomycin A1) significantly promoted the cytotoxicity of ZnO NPs and inhibited the cytoprotective effects of CC. In conclusion, these data suggest that CC could modestly protect Caco-2 cells from ZnO NP exposure, probably through the induction of autophagy.
研究领域:
毒理学
·
细胞生物学
·
药理学
·
纳米技术
✓ 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）