PHYSIOLOGICAL RESEARCH
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2023
·
IF 2.1
Qiying JIN,Zhengnan LI,Qian XU,Qian LIU
Matrine is an active ingredient in traditional Chinese medicine that has been shown to be effective in treating bone disorders. The anti-osteoarthritis (OA) effects of matrine were assessed using both in in vitro and in vivo systems, and the mechanisms underlying the effects were investigated by focusing on the activity of miR-29b-3p/PGRN axis. The miR was chosen as potential target for matrine after chondrocytes were treated with both IL-1β and matrine. Changes in cell viability, cell apoptosis, inflammation, and miR-29b-3p/PGRN axis were detected. In vitro assays results were validated using collagen-induced arthritis (CIA) rat models. Incubation with IL-1β reduced cell viability, induced cell apoptosis, and inhibited production of cytokines in chondrocytes, which was associated with the up-regulation of miR-29b-3p and down-regulation of PGRN. In CIA rats, matrine reduced bone destruction and weight loss in a dose-dependent manner. Matrine also reduced the systemic levels of cytokines. At the molecular level, matrine inhibited the expression of miR-29b-3p while increasing the expression of PGRN. The findings outlined in the current study showed that matrine exerted its anti-OA effects by modulating the miR-29b-3p/PGRN axis.
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Frontiers in Cardiovascular Medicine
·
2022
·
IF 5.846
Chen Cong,Liu Shuhong,Cao Gaozhen,Hu Yang,Wang Run,Wu Min,Liu Mingya,Yiu Kai Hang
Background: This study primarily explored the role of paeonol in doxorubicin (DOX)-induced chronic heart failure (CHF), considering the cardioprotective effect of paeonol on an epirubicin-induced cardiac injury.Methods: DOX-induced CHF-modeled rats were treated with paeonol. Cardiac function and myocardial damage in rats were evaluated by using the multifunction instrument, and the histopathology, apoptosis, and the expression of miR-21-5p and S-phase kinase-associated protein 2 (SKP2) in myocardium were detected. The target gene of miR-21-5p was confirmed by a dual-luciferase reporter assay. After the required transfection or paeonol treatment, the viability, apoptosis, mitochondrial membrane potential (MMP), and reactive oxygen species (ROS) of the DOX-induced cardiomyocytes were determined. Reverse-transcription quantitative-PCR (RT-qPCR) and Western blot were performed to quantify the expressions of miR-21-5p, SKP2, and apoptosis-related factors.Results: Paeonol improved cardiac function and also ameliorated the cardiac damage of CHF-modeled rats, where the downregulation of abnormally elevated myocardial damage markers, including brain natriuretic peptide, lactate dehydrogenase, renin, angiotensin II, aldosterone, and endothelin 1, was observed. Paeonol alleviated the histopathological injury and suppressed the apoptosis in CHF-modeled rats, inhibited miR-21-5p expression, and upregulated SKP2 expression in vitro and in vivo. miR-21-5p targeted SKP2. Paeonol and SKP2 increased the viability and MMP, but reduced apoptosis and ROS in the DOX-induced cardiomyocytes. miR-21-5p exerted effects opposite to PAE and SKP2, and it downregulated the expression of Bcl-2 and mitochondrion-Cytochrome c (Cyt c) and upregulated the expression of Bax, C-caspase-3, and cytoplasm-Cyt c. miR-21-5p reversed the effects of paeonol, and its effects were further reversed by SKP2.Conclusion: Paeonol shows a cardioprotective effect on DOX-induced CHF via regulating the miR-21-5p/SKP2 axis.- Paeonol inhibited miR-21-5p expression in doxorubicin-induced chronic heart failure rats and in doxorubicin-induced cardiomyocytes.- SKP2 was targeted by miR-21-5p and it was down-regulated in chronic heart failure rats and doxorubicin-induced cardiomyocytes.- Paeonol showed cardioprotective effects on doxorubicin-induced chronic heart failure via regulating miR-21-5p/SKP2/PI3K/AKT axis.
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Epigenomics
·
2022
·
IF 4.357
Hanlin Li,Yanjie Yang,Jianpeng Yu,Boya Zhang,Xuanrong Chen,Shimiao Zhu,Yuanjie Niu,Zhiqun Shang
Aims: We aimed to determine whether intronic circRNA acts as a molecular sponge in castration-resistant prostate cancer (CRPC). Materials & methods: A gene chip technique was used to conduct sequencing. A qPCR experiment was performed to verify the result. Radioimmunoprecipitation, RNA pull-down and dual-luciferase reporter assays were performed to particularly expound its function. Verification of downstream effects was carried out through qPCR and western blot, and a xenograft assay was performed in vivo for verification. Results: Intronic circRNA hsa_circ_0092339 in the nucleus was highly expressed in CRPC cell lines. hsa_circ_0092339 did not regulate the expression of its parental gene. hsa_circ_0092339 functions like a molecular sponge, preventing degradation of C-MYC mRNA by absorbing hsa-mir-940. Conclusion: hsa_circ_0092339 plays a critical role in CRPC through targeting C-MYC indirectly by absorbing hsa-mir-940.Plain language summaryOur research breaks the mold by investigating a novel function of RNA and a novel regulatory mechanism. Our research provides a new therapeutic target for prostate cancer treatment and broadens the understanding of prostate cancer.
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SCIENCE OF THE TOTAL ENVIRONMENT
·
2022
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IF 10.753
Chenxi Zhao,Ruihui Xie,Qiuhui Qian,Jin Yan,Huili Wang,Xuedong Wang
As a broad-spectrum antibacterial agent, triclosan (TCS) has been confirmed to possess potential immunotoxicity to organisms, but the underlying mechanisms remains unclear. Herein, with the aid of transgenic zebrafish strains Tg ( coro 1A: EGFP) and Tg ( rag 2: DsRed), we intuitively observed acute TCS exposure caused the drastic differentiation, abnormal development and distribution of innate immune cells, as well as barriers to formation of adaptive immune T cells. These abnormalities implied occurrence of the cytokine storm, which was further evidenced by expression changes of immune-related genes, and functional biomarkers. Based on transcriptome deep sequencing, target gene prediction and dual luciferase validation, the highly conservative and up-regulated miR-19a was chosen as the research target. Under TCS exposure, miR-19a up-regulation triggered down-regulation of its target gene socs3b , and simultaneously activated the downstream IL-6/STAT3 signaling pathway. Artificial over-expression and knock-down of miR-19a was realized by microinjecting agomir and antagomir, respectively, in 1–2-cell embryos. The miR-19a up-regulation inhibited socs3b expression to activate IL-6/STAT3 pathway, and yielded abnormal changes in the functional cytokine biomarkers, along with the sharp activation of immune responses. These findings disclose the molecular mechanisms regarding TCS-induced immunotoxicity, and offer important theoretical guidance for healthy safety evaluation and disease early warning from TCS pollution.
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IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL
·
2022
·Vol. 58
·期 2
·96-108
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IF 2.723
Sun Xiaogang,Hou Zhiyun,Li Ning,Zhang Shuangwei
Hepatocellular carcinoma (HCC) is the most common primary liver cancer with high incidence and mortality. MiR-597-5p is downregulated in tumor tissues of HCC compared with non-tumor tissues. However, its role in HCC is still unknown. This study aims to assess the function of miR-597-5p in HCC development and investigate the underlying mechanism. To perform gain- and loss-of-function studies, SK-HEP-1 cells and Huh-7 cells were transfected with miR-597-5p mimics and inhibitor, respectively. MiR-597-5p markedly reduced the cell viability and the expression of Ki-67 in HCC cells. MiR-597-5p also repressed the cell cycle progression of HCC cells and the protein levels of cyclin D1 and CDK2. Moreover, miR597-5p inhibited the migration and invasion of HCC cells and decreased MMP2 and MMP9 levels. Transcriptional enhancer associate domain transcription factor 1 (TEAD1) was identified as a target of miR-597-5p by luciferase reporter assay. TEAD1 and its downstream target genes, CTGF and CYR61, were downregulated by miR-597-5p in HCC cells. Furthermore, miR-597-5p was demonstrated to function in HCC progression by targeting TEAD1 via TEAD1 expression gain and loss. Our study demonstrates that miR-597-5p represses the proliferation, migration, and invasion of HCC cells through targeting TEAD1, which provides a therapeutic target for HCC treatment.
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INTERNATIONAL IMMUNOPHARMACOLOGY
·
2023
·
IF 5.6
Yao Guo,Jing Cui,Xueyi Liang,Taoyu Chen,Chong Lu,Tao Peng
Pancreatic cancer (PC) is a serious threat to human health, with most patients diagnosed at the advanced stages of the disease. Treatment with gemcitabine (GEM) leads to PC GEM resistance. In addition, cancer stem cell (CSC)-derived exosomes play an important role in cancer progression. We aimed to investigate the role and mechanism of action of PC stem cell-derived exosomes in PC drug resistance and progression. CSC-derived exosomes increased the proportion of F4/80+/CD86 + cells and levels of M2 polarization factors. miR-210 is expressed in CSC-derived exosomes. Thus, following co-culture, miR-210 was taken up by macrophages. Transfection or the addition of miR-210 mimics increased the proportion of F4/80+/CD206 + cells and levels of M2 polarization factors. Further, the miR-210 targets inhibited the levels of FGFRL1. The FGFRL1 overexpression plasmid also inhibited miR-210-mediated M2 polarization. After co-culture of THP-M2 cells with PC cells and treatment with GEM, the survival rate, migration rate, and levels of MDR, YB-1, BCRP, p-PI3K, p-AKT, and p-mTOR in PC cells increased. And THP-M2 increased the tumor volume and MDR, YB-1, BCRP, p-PI3K, p-AKT, and p-mTOR levels. Overall, miR-210 from PC stem cell-derived exosome targets and inhibits FGFRL1 to promote macrophage M2 polarization, which activates the p-PI3K/p-AKT/p-mTOR pathway and increases GEM resistance.
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ENVIRONMENTAL TOXICOLOGY
·
2023
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IF 4.5
Weipu Mao,Lei Zhang,Yiduo Wang,Si Sun,Jianping Wu,Jie Sun,Xiangyu Zou,Ming Chen,Guangyuan Zhang
Cisplatin nephrotoxicity is an etiological factor for acute kidney injury (AKI). MicroRNA (miRNA) expression is dysregulated in cisplatin-induced AKI (cAKI) although the underlying mechanisms are unclear. A cAKI model was established by intraperitoneally injecting cisplatin, and key miRNAs were screened using high-throughput miRNA sequencing. The functions of key miRNAs were determined using the cell viability, live/dead, reactive oxygen species (ROS), and 5-ethynyl-2′-deoxyuridine (EdU) proliferation assays. Additionally, the macrophage membrane was wrapped around a metal–organic framework (MOF) loaded with miRNA agomir to develop a novel composite material, macrophage/MOF/miRNA agomir nanoparticles (MMA NPs). High-throughput miRNA sequencing revealed that miR-30e-5p is a key miRNA that is downregulated in cAKI. The results of in vitro experiments demonstrated that miR-30e-5p overexpression partially suppressed the cisplatin-induced or lipopolysaccharide (LPS)-induced downregulation of cell viability, proliferation, upregulation of ROS production, and cell death. Meanwhile, the results of in vivo and in vitro experiments demonstrated that MMA NPs alleviated cAKI by exerting anti-inflammatory effects. Mechanistically, cisplatin downregulates the expression of miR-30e-5p, and the downregulated miR-30e-5p can target Galnt3 to activate the adenosine 5‘-monophosphate activated protein kinase (AMPK) signaling pathway, which promotes the progression of AKI. Our study found that miR-30e-5p is a key downregulated miRNA in cAKI. The downregulated miR-30e-5p promotes AKI progression by targeting Galnt3 to activate the AMPK signaling pathway. The newly developed MMA NPs were found to have protective effects on cAKI, suggesting a potential novel strategy for preventing cAKI.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2023
·
IF 8.2
Lin Peng,Shasha Chen,Hongjin Lin,Chunyan Wan,Xiang Li,Shiwen Xu,Shu Li
Bisphenol A (BPA) is an endocrine disruptor. Excessive BPA intake can damage the structure and function of the respiratory tract. Dietary selenium (Se) deficiency may also cause immune tissue damage. To investigate the potential mechanism of BPA on tracheal damage in selenium-deficient chickens and the role of microRNAs (miRNAs) in this process, we established in vitro and in vivo Se deficiency and BPA exposure models and screened out miR-155 for follow-up experiments. We further predicted and confirmed the targeting relationship between miR-155 and TRAF3 using TargetScan and dual luciferase assays and found that miR-155 was highly expressed and caused inflammatory damage. Further studies showed that BPA exposure increased airway oxidative stress, activated the NF-κB pathway, and caused inflammation and immune damage in selenium-deficient chickens, but down-regulating miR-155 and NAC treatment could reverse this phenomenon. This suggested that these pathways are regulated by the miR-155/TRAF3/ROS axis. In conclusion, BPA exposure aggravates airway inflammation in selenium-deficient chickens by regulating miR-155/TRAF3/ROS. This study revealed the mechanism of BPA exposure combined with Se deficiency in tracheal inflammatory injury in chickens and enriched the theoretical basis of BPA injury in poultry.
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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.
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TOXICOLOGY LETTERS
·
2021
·
IF 4.374
Shanqi Guo,Yangyi Zhang,Shuo Wang,Tong Yang,Baojie Ma,Xiaojiang Li,Yizhuo Zhang,Xingkang Jiang
Antimony is a common environmental contaminant that causes biological toxicity in exposed populations worldwide. Previous studies have revealed that antimony promotes prostate cancer growth by stabilizing the c-Myc protein and mimicking androgen activity. However, the role of lncRNAs in the regulation of antimony-induced carcinogenesis remains unknown, and the precise mechanisms need to be explored. In the present study, we found that chronic exposure to antimony promoted cell growth and lipid metabolic disequilibrium in prostate cancer. Mechanistically, we identified a long noncoding RNA molecule, PCA3, that was substantially upregulated in LNCaP cells in response to long-term antimony exposure. Functional studies indicated that abnormal PCA3 expression modulated antimony-induced proliferation and cellular triglyceride and cholesterol levels. In addition, PCA3 levels were found to be inversely correlated with MIR-132-3 P levels by acting as a decoy for MIR-132-3P. Besides, SREBP1 directly interacted with MIR-132-3 P to increase cell growth and disrupt lipid metabolism by targeting its 3’UTR regions. Taken together, our results revealed that lncRNA PCA3 promotes antimony-induced lipid metabolic disorder in prostate cancer by targeting MIR-132-3 P/SREBP1 signaling.
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ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2021
·
IF 6.291
Yangyi Zhang,Shanqi Guo,Shuo Wang,Xiaojian Li,Dingkun Hou,Hongzheng Li,Lili Wang,Yong Xu,Baojie Ma,Haitao Wang,Xingkang Jiang
Previous studies suggest that cadmium (Cd) is one of the causative factors of prostate cancer (PCa), but the effect of chronic Cd exposure on PCa progression remains unclear. Besides, whether long noncoding RNAs (lncRNAs) are involved in the regulation of prolonged exposure to Cd in PCa needs to be elucidated. In the present study, we found that the serum concentration of Cd in PCa patients was positively correlated with the Gleason score and tumor-node-metastasis (TNM) classification. To simulate chronic Cd exposure in PCa, we subjected PC3 and DU145 cells to long-term, low-dose Cd exposure and further examined tumor behavior. Functional studies identified that chronic Cd exposure promoted cell growth and ferroptosis resistance in vitro and in vivo. Furthermore, we found that lncRNA OIP5-AS1 expression was greatly elevated in PC3 and DU145 cells upon chronic Cd exposure. Dysregulation of OIP5-AS1 expression mediated cell growth and Cd-induced ferroptosis. Mechanistically, we demonstrated that OIP5-AS1 served as an endogenous sponge of miR-128-3p to regulate the expression of SLC7A11, a surrogate marker of ferroptosis. Moreover, miR-128-3p decreased cell viability by enhancing ferroptosis. Taken together, our data indicate that lncRNA OIP5-AS1 promotes PCa progression and ferroptosis resistance through miR-128-3p/SLC7A11 signaling.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2020
·
IF 5.162
Jia-Qi He,Min-Xia Zheng,Hua-Zhong Ying,Yu-Sen Zhong,Huan-Huan Zhang,Min Xu,Chen-Huan Yu
Two polysaccharides (PRP1 and PRP2) were isolated from Platycodonis Radix . Preliminary structural analysis indicated that PRP1 was composed of glucose, fructose, and arabinose in a molar ratio of 1:1.91:1.59 with a molecular weight of 440 kDa, whereas PRP2 was composed of arabinose, fructose, and galactose in a molar ratio of 1:1.39:1.18 with a molecular weight of 2.85 kDa. Compared with PRP2, PRP1 exerted stronger anticancer activity in vitro. Treatment with 5–30 μg/ml of PRP1 significantly inhibited the proliferation of HepG2 cells in vitro, and oral administration at the doses of 75–300 mg/kg also reduced the tumor growth in vivo. The miRNA expression patterns of human liver cancer cells HepG2 in vivo under PRP1 treatment were established, and microRNA-21 (miR-21) as the onco-miRNA was appreciably downregulated. PRP1 repressed the expression of miR-21, which directly targeted and suppressed PTEN (a negative regulator of the PI3K/Akt signaling cascade), and subsequently upregulated the expression of PTEN but downregulated the PI3K/AKT pathway, thereby promoting liver cancer cell apoptosis. These findings indicated that PRP1 inhibited the proliferation and induced the apoptosis of HepG2 mainly via inactivating the miR-21/PI3K/AKT pathway. Therefore, PRP1 could be used as a food supplement and candidate for the treatment of liver cancer.
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