BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
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2023
·
IF 5.1
Ziyuan Tong,Yuan Shen,Quan Yuan,Honghao Yu
Despite recent advances in understanding the biological behavior of osteosarcoma (OS), OS is still the most common primary bone sarcoma that endangers the health of children and adolescents. High-temperature requirement A (HTRA) protease family plays an important regulatory role in numerous malignancies and acts as a prognostic biomarker. However, the function and underlying mechanisms of the HTRA family in OS development remain unknown. Through analyzing the GSE126209 dataset obtained from different Gene Expression Omnibus (GEO) databases, we found that HTRA3 as a member of the HTRA family was downregulated in OS tissues compared with that in normal tissues. Functional experiments indicated that HTRA3 overexpression suppressed malignant behaviors of OS cells in vitro and tumor growth in vivo . Mechanistically, we found that HTRA3 co-localized with the X-linked inhibitor of apoptosis protein (XIAP) and decreased XIAP stability. Further investigation showed that XIAP knockdown inhibited the degradation of phosphatase and tensin homolog (PTEN) and that HTRA3 caused the blockage of PTEN/phosphoinositide 3-kinase (PI3K)/AKT pathway, characterized as the reverse of cell function caused by HTRA3 overexpression after PTEN inhibitor BpV (HOpic) treatment. Detailed investigations showed that forkhead box protein 1 (FOXP1), an oncogene in OS progression, downregulated HTRA3 expression and inhibited the transcriptional activity of HTRA3 , suggesting that HTRA3 was regulated negatively by FOXP1. In conclusion, our study demonstrates that HTRA3 is a repressor involved in OS development via the PTEN/PI3K/AKT pathway under the modulation of transcription factor FOXP1, and it may provide a therapeutic direction for OS patients.
研究领域:
肿瘤学
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分子生物学
·
癌症研究
·
细胞生物学
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产品关联
DOI
PubMed
高影响因子
Molecular Medicine Reports
·
2020
·Vol. 22
·期 5
·3944-3954
·
IF 2.1
Li Zhu,Xueying Zhou,Shanshan Li,Jianmeng Liu,Jingyan Yang,Xiangyun Fan,Shengnian Zhou
Cerebral ischemia is a common cerebrovascular disease caused by the occlusion of a cerebral blood vessel. MicroRNAs (miRNAs/miRs) are emerging regulators of various human diseases, including cerebral ischemia. Upregulation of miR‑183‑5p has been reported to alleviate liver injury induced by ischemia‑reperfusion (I/R). However, the effect of miR‑183‑5p on cerebral ischemia injury remains unknown. The present study evaluated the effects of miR‑183‑5p on ischemia injury using ischemic models of mouse brains exposed to transient middle cerebral artery occlusion and Neuro‑2A (N2A) neuroblastoma cells exposed to oxygen‑glucose‑deprivation (OGD) and subsequently reoxygenated. Ischemia was evaluated in mice using neurological function scores, cerebral edema, 2,3,5‑triphenyltetrazoliumchloride, Nissl and Fluoro‑Jade B staining assays. In addition, miR‑183‑5p expression, N2A cell viability and the expression levels of apoptosis‑associated proteins were detected by quantitative PCR, Cell Counting Kit‑8 assay, flow cytometry and western blotting. The association between miR‑183‑5p and phosphatase and tensin homolog (PTEN) was also confirmed by a luciferase reporter assay. The results revealed that miR‑183‑5p expression was decreased and brain damage was increased in ischemic mice compared with the sham group. Additionally, miR‑183‑5p levels were reduced, and apoptosis was increased in N2A cells exposed to ischemia compared with the control group. Following transfection with agomiR‑183‑5p, cerebral ischemic injury and apoptosis levels were reduced in the in vivo I/R stroke model and OGD‑induced N2A cells. In addition, PTEN was determined to be a target of miR‑183‑5p following elucidation of a direct binding site. Overexpression of PTEN reversed the miR‑183‑5p‑induced N2A cell apoptosis inhibition and survival after OGD. The results of the present study suggested that miR‑183‑5p reduced ischemic injury by negatively regulating PTEN, which may aid the development of a novel therapeutic strategy for cerebral ischemia.
研究领域:
神经科学
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分子生物学
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医学研究
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DOI
PubMed
高影响因子
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
·
2020
·Vol. 146
·期 4
·875-882
·
IF 3.656
Wang Maonan,Wang Lishan,Feng Huan,Jiang Hui,Zhou Jiahua,Wang Xuemei
Purpose Presently, liver cancer is still one of the malignant tumors with high mortality. As far as the treatment of liver cancer is concerned, the most effective method is still liver transplantation. But every year, many liver cancer patients die from the lack of a proper liver transplant, or from waiting for a liver transplant. Therefore, it is very important to find new and effective treatment for patients with liver cancer. Methods Herein, the cell model and the orthotropic liver tumor mice model have been performed to verify the results of our treatment. We found that the in situ synthesized gold nanocluster–PTEN (GNC–PTEN) complexes can effectively target and realize the fluorescence imaging of the liver tumor. Results GNC–PTEN complexes could inhibit the proliferation, invasion, and metastasis of liver cancer cells. And the results also showed that GNC–PTEN complexes could be well targeted liver tumor at 6 h and the liver tumor in mice group treated with GNC–PTEN complexes almost disappeared. Conclusion This is a simply and effectively method to realize liver cancer imaging and inhibition. This may raise the possibility for the accurate image/diagnosis and simultaneously efficient treatment of liver cancer in the relevant clinic application.
研究领域:
肿瘤学
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分子生物学
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纳米医学
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产品关联
DOI
PubMed
高影响因子
Journal of Cancer
·
2020
·
IF 3.565
Yadong Liu,Fanlu Lin,Yaodong Chen,Rui Wang,Jiannan Liu,Yinshan Jin,Ruihua An
Cryptotanshinone (CTT), extracted from the root of Salvia miltiorrhiza Bunge (Danshen), exhibits activities against a variety of human cancers in vitro and in vivo . The purpose of this study was to investigate the potential inhibitory effect of CTT on bladder cancer. In this study, we found that CTT inhibited bladder cancer cell proliferation, migration, and invasion and promoted apoptosis. In addition, CTT modulated the expression of proteins via the PI3K/AKT pathway, and the inhibition of PI3K/AKT signalling was due to induction of PTEN expression. Taken together, the results of the present study demonstrated the anticancer effect of CTT on bladder cancer cells, which might be associated with the downregulation of PI3K/AKT/mTOR and NF-κB signalling pathway proteins, and this inhibition was mediated by the induction of PTEN.
研究领域:
肿瘤学
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药理学
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细胞生物学
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DOI
PubMed
高影响因子
Journal of Orthopaedic Surgery and Research
·
2020
·Vol. 15
·期 1
·1-8
·
IF 1.777
Zhang Wei,Cui Sheng-Yu,Yi Hong,Zhu Xin-Hui,Liu Wei,Xu You-Jia
Background The dysregulation of proliferation and apoptosis plays a significant role in the pathogenesis of postmenopausal osteoporosis (PO). MicroRNAs play an important role in regulating apoptosis of MC3T3-E1 cells. However, the role and potential mechanism of miR-708 for regulating H2O2-induced apoptosis is unknown. This study aimed to investigate the protective function of miR-708 in H2O2-induced apoptosis of MC3T3-E1 osteoblasts.Methods MC3T3-E1 was co-cultured with H2O2 for 8 h, then, flow cytometry, malondialdehyde (MDA), and glutathione peroxidase (Gpx) levels were measured to establish the oxidative model. MiRNA microarray was performed to assess differentially expressed miRNAs between control and H2O2-treated MC3T3-E1 cells. We then performed RT-PCR to identify the relative expression of miR-708 and PTEN. After transfected MC3T3-E1 with miR-708 mimics, flow cytometry, MDA, and Gpx level were performed to identify the apoptosis rate and oxidative stress in these groups. Furthermore, we small interfering RNA of PTEN to identify the role of PTEN in H2O2-induced apoptosis of MC3T3-E1 cells.Results H2O2 (100 nM) could significantly induce the apoptosis of MC3T3-E1 cells. Moreover, H2O2 could significantly increase the MDA level and downregulated Gpx level. RT-PCR found that H2O2 significantly decrease the level of miR-708. Compared with H2O2 group, H2O2 + miR-708 mimic significantly decreased the apoptosis rate.Conclusion smiR-708 plays a protective role in H2O2-induced MC3T3-E1 osteoblasts apoptosis and its protective effect is proceeded by regulating ROS level and PTEN expression level.
研究领域:
分子生物学
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细胞生物学
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骨质疏松研究
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产品关联
DOI
PubMed
高影响因子
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
·
2017
·
IF 4.521
Jing Zhang,Li Li,Yueting Peng,Yu Chen,Xiaoying Lv,Shun Li,Xiang Qin,Hong Yang,Chunhui Wu,Yiyao Liu
Tumor cell can be significantly influenced by various chemical groups of the extracellular matrix proteins. However, the underlying molecular mechanisms involved in the interaction between cancer cells and functional groups in the extracellular matrix remain unknown. Using chemically modified surfaces with biological functional groups (CH 3 , NH 2 , OH), it was found that hydrophobic surfaces modified with CH 3 and NH 2 suppressed cell proliferation and induced the number of apoptotic cells. Mitochondrial dysfunction, cytochrome c release, Bax upregulation, cleaved caspase-3 and PARP, and Bcl-2 downregulation indicated that hydrophobic surfaces with CH 3 and NH 2 triggered the activation of intrinsic apoptotic signaling pathway. Cells on the CH 3 - and NH 2 -modified hydrophobic surfaces showed downregulated expression and activation of integrin β1, with a subsequent decrease of focal adhesion kinase (FAK) activity. The RhoA/ROCK/PTEN signaling was then activated to inhibit the phosphorylation of PI3K and AKT, which are essential for cell proliferation. However, pretreatment of MDA-MB-231 cells with SF1670, a PTEN inhibitor, abolished the hydrophobic surface-induced activation of the intrinsic pathway. Taken together, the present results indicate that CH 3 - and NH 2 -modified hydrophobic surfaces induce mitochondria-mediated apoptosis by suppressing the PTEN/PI3K/AKT pathway, but not OH surfaces. These findings are helpful to understand the interaction between extracellular matrix and cancer cells, which might provide new insights into the mechanism potential intervention strategies for tumor prognosis.
研究领域:
癌症生物学
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细胞生物学
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分子生物学
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生物化学
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产品关联
DOI
PubMed
高影响因子
EXPERIMENTAL PHYSIOLOGY
·
2020
·Vol. 105
·期 11
·1918-1927
·
IF 2.431
Manfeng Wang,Xiaowei Wu,Lu Gan,Zongyan Teng,Haijin Zhang,Yina Zhang
New Findings What is the central question of this study? Does Dnmt3a play a crucial role in regulating diabetic muscle atrophy? What is the main finding and its importance? Muscle atrophy is one of the major long-term complications of diabetes mellitus. However, little is known about the molecular mechanism involved. In this paper, we demonstrated that Dnmt3a overexpression effectively improves the diabetic muscle health in mice and documented the underlying mechanisms. DNMT3A might become a promising target to prevent muscle atrophy in patients with diabetes. Muscle atrophy is one of the major long-term complications of diabetes mellitus, which greatly affects the mobility of patients. Epigenetic processes mediated by DNA methyltransferases (DNMTs) play crucial roles in the locomotor system, but little is known about the functions of DNMTs in diabetic muscle atrophy. Here, we investigated the function of Dnmt3a in diabetic muscle atrophy and explored the mechanisms involved. Adeno-associated virus AAV2 overexpressing Dnmt3a or its vector control was injected into the tibialis anterior muscle of streptozotocin-induced diabetic mice. Muscle mass and muscle cross-sectional area were used to evaluate muscle atrophy. In vitro , adeno-associated virus AAV2 overexpressing Dnmt3a or its vector control was transfected into C2C12 myoblasts. Horse serum was used to induce differentiation and palmitate to stimulate the C2C12 myoblasts. The expressions of myogenic regulatory factors were examined by real-time PCR and western blot analysis. Overexpression of Dnmt3a attenuated muscle atrophy in diabetic mice and promoted myotube formation of C2C12 myoblasts. Overexpression of Dnmt3a restored the expressions of myogenic regulatory factors atrogin-1, MuRF1, Pax7, Myod1 and myogenin, both in vivo and in vitro . Moreover, overexpression of Dnmt3a activated the phosphorylation of Akt by inhibiting the activation of Pten. This study demonstrates that overexpression of Dnmt3a prevents diabetic muscle atrophy by modulating the Pten/Akt pathway.
研究领域:
分子生物学
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糖尿病
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肌肉生理学
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表观遗传学
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产品关联
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2021
·
IF 6.291
Luyao Li,Mei Zhou,Biyun Chen,Qin Wang,Shuya Pan,Yaxuan Hou,Jiamin Xia,Xue Zhou
Cadmium is a carcinogenic heavy metal that poses a severe threat to human beings. The underlying mechanism, however, remains elusive. N6-methyladenosine (m6A) is the most abundant post-transcriptional modification in mRNA that regulates RNA metabolism. Emerging evidence shows that m6A is involved in the pathogenesis of various cancers. In this study, human bronchial epithelial BEAS-2B cells were transformed by exposing to 2 μM of cadmium for 20 weeks to investigate the role of m6A in cadmium carcinogenesis. We found the level of m6A in mRNA was significantly decreased in cadmium-transformed BEAS-2B cells, and this change was regulated by m6A demethylase ALKBH5. ALKBH5 was significantly upregulated in the middle and late stages of cell transformation at week 8, 12, 16 and 20. Knockdown of ALKBH5 in cadmium-transformed cells alleviated cell proliferation, migration, invasion, and anchorage-independent growth, but co-transfection with ALKBH5 siRNA and PTEN siRNA restored the inhibitory effects of ALKBH5 knockdown on those transformation properties. ALKBH5 decreased the m6A level of PTEN mRNA, resulting in its instability and reduction of PTEN protein expression. These results indicate that ALKBH5-mediated demethylation m6A at PTEN mRNA is involved in cadmium-induced cell transformation. Our study provides a new perspective for the involvement of m6A modification in cadmium carcinogenesis.
研究领域:
毒理学
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分子生物学
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癌症研究
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2022
·
IF 5.714
Xin Chen,Sai Zhu,Si-Yu Chen,Jia-Nan Wang,Li-Jiao Sun,Shan-Min Tao,Xiao-Feng Li,Hai-Di Li,Ying-Yin Sun,Chuan-Hui Xu,Xiao-Guo Suo,Ming-Lu Ji,Cheng Huang,Xiao-Ming Meng,Jun Li
Hepatic fibrosis is an essential pathology of multiple chronic liver diseases. The aim of this study was to investigate the role of miR-301a-3p in hepatic fibrosis. We found that miR-301a-3p was upregulated in hepatic fibrosis patients and in culture-activated human hepatic stellate cells (HSCs). Interestingly, miR-301a-3p expression was increased in hepatic fibrosis progression mice while decreased in hepatic fibrosis recovery mice, indicating that miR-301a-3p may participate in the hepatic fibrosis pathology. Functionally, the effects of miR-301a-3p both on hepatic fibrosis progression and regression were assessed in vivo . Inhibiting miR-301a-3p ameliorated mouse liver fibrogenesis and collagen deposition and suppressed HSC activation and fibrogenic factor expression. Whereas, in hepatic fibrosis regression, upregulating miR-301a-3p impaired mouse hepatic fibrosis recovery by inducing HSC activation and triggering inflammation. Consistently, gain-of-function and loss-of-function analysis of miR-301a-3p were performed to evaluate its effects on human HSCs LX-2 cell. We found that suppressing miR-301a-3p inhibited LX-2 cell activation and proliferation, and induced LX-2 cell apoptosis, accompanied by decreased fibrotic mediators expression. Collectively, these findings suggest miR-301a-3p drives liver fibrogenesis and HSC activation in hepatic fibrosis. Mechanistically, we demonstrated miR-301a-3p binds directly to phosphatase and tensin homolog (PTEN) by luciferase reporter analysis, pull-down, and RIP assay. Indicating that miR-301a-3p plays a critical role in promoting liver fibrogenesis via modulating the PTEN/platelet derived growth factor β (PDGFR-β) pathway. In conclusion, our findings demonstrate that miR-301a-3p expression is closely correlated with hepatic fibrosis pathology, and that enhancing miR-301a-3p maintains the HSC profibrogenic phenotype, triggers inflammatory responses, promotes fibrogenic factor production, and further exacerbates liver fibrogenesis. These findings suggest that miR-301a-3p may serve as a promising diagnostic and prognosis biomarker for hepatic fibrosis treatment.
研究领域:
分子生物学
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肝病学
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
HUMAN GENE THERAPY
·
2020
·
IF 4.51
Kaihua Zhai,Boyu Liu,Lin Gao
Long-noncoding RNA taurine upregulated gene 1 (TUG1) participates in nervous system diseases, but its function in Parkinson's disease (PD) remains unclear. This study explored the function and mechanism of TUG1 in PD. A PD model was constructed using SH-SY5Y cells induced by 1-methyl-4-phenylpyridinium (MPP+) in vitro and mice treated by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in vivo. The expressions of TUG1, miR-152-3p, phosphatase and tensin homologue (PTEN), tyrosine hydroxylase (TH), and Bcl-2, and cleaved caspase-3 expressions were determined by quantitative reverse transcription-PCR and Western blotting. The viability, apoptosis, reactive oxygen species, and release of inflammatory factors from SH-SY5Y cells and substantia nigra tissues were detected by commercial kits. The interaction between TUG1 and miR-152-3p was analyzed by dual-luciferase reporter assay. Hematoxylin/eosin and immunohistochemical staining was performed for assessing the pathological damage and proportion of TH-positive cells. In PD cell model and mice model, TUG1 expression was upregulated and that of miR-152-3p was downregulated. Further research showed that TUG1 sponged and regulated miR-152-3p expression. Silencing of TUG1 not only protected SH-SY5Y cells against cell apoptosis, oxidative stress, and neuroinflammation in vitro, pathological damage and neuroinflammation in vivo, but also suppressed the expressions of PTEN and cleaved caspase-3, and increased the expressions of TH and Bcl-2 in MPP+-treated SH-SY5Y cells. However, the protective role of siTUG1 in SH-SY5Y cells was significantly inhibited by the miR-152-3p inhibitor. Thus, knocking down TUG1 might have a protective effect on PD through the miR-152-3p/PTEN pathway.
研究领域:
神经科学
·
分子生物学
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病理学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
·
2020
·Vol. 24
·期 18
·11001-11011
·
IF 4.486
Jun Liu,Jinli Ding,Bing Qu,Jiuying Liu,Xiaojie Song,Qingli Suo,Aifen Zhou,Jing Yang
Polycystic ovary syndrome (PCOS), the most common female endocrine disease that causes anovulatory infertility, still lacks promising strategy for the accurate diagnosis and effective therapeutics of PCOS attributed to its unclear aetiology. In this study, we determined the abnormal reduction in circPSMC3 expression by comparing the ovarian tissue samples of PCOS patients and normal individuals. The symptom relief caused by up-regulation of circPSMC3 in PCOS model mice suggested the potential for further study. In vitro functional experiments confirmed that circPSMC3 can inhibit cell proliferation and promote apoptosis by blocking the cell cycle in human-like granular tumour cell lines. Mechanism study revealed that circPSMC3 may play its role through sponging miR-296-3p to regulate PTEN expression. Collectively, we preliminarily characterized the role and possible insights of circPSMC3/miR-296-3p/PTEN axis in the proliferation and apoptosis of KGN cells. We hope that this work provides some original and valuable information for the research of circRNAs in PCOS, not only to better understand the pathogenesis but also to help provide new clues for seeking for the future therapeutic target of PCOS.
研究领域:
妇科学
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分子生物学
·
内分泌学
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产品关联
DOI
PubMed
高影响因子
Oncology Letters
·
2019
·Vol. 18
·期 4
·3553-3560
·
IF 1.871
Quanliang Li,Shuya Zhang,Mingyu Wang,Shouguang Dong,Yan Wang,Song Liu,Tiancheng Lu,Yuqin Fu,Xiuran Wang,Guihong Chen
Matrine is an alkaloid extracted from the leguminous plant Sophora flavescens. Matrine has clinical effects in the treatment of tumors, including those in lung cancer, nasopharyngeal cancer and liver cancer. However, the effect of matrine on follicular thyroid cancer has not been reported. The aim of the present study was to investigate the effect of matrine on follicular thyroid cancer and its potential mechanism. FTC‑133 follicular thyroid cancer cells were treated with different concentrations of matrine, and an MTT assay showed that matrine inhibited the growth of FTC‑133 cells in a dose‑ and time‑dependent manner with an IC50 value of 154.8 µM. Cell apoptosis was analyzed by flow cytometry and the results showed that matrine effectively induced the apoptosis of FTC‑133 cells. The expression level of microRNA (miR)‑21 was analyzed by reverse transcription‑quantitative PCR (RT‑qPCR) analysis, and the mRNA and protein expression levels of PTEN, Akt and phosphorylated (p)‑Akt were detected by RT‑qPCR analysis and western blotting, respectively. The expression of miR‑21 was significantly downregulated, PTEN was upregulated at the mRNA and protein expression levels, and p‑Akt was downregulated in the FTC‑133 cells. The effects of miR‑21 mimics and miR‑21 inhibitor on the expression of miR‑21, PTEN and Akt in FTC‑133 cells, and the effect of miR‑21 mimics/matrine on the expression of PTEN were also investigated. The results of the present study suggested that matrine inhibited the growth and induced apoptosis of FTC‑133 cells via the miR‑21/PTEN/Akt signaling pathway.
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
危险品化学品经营许可证（带存储）