CELL BIOLOGY AND TOXICOLOGY
·
2021
·Vol. 37
·期 4
·633-651
·
IF 6.691
Zhao Peng,Cheng Jianhua,Li Bin,Nie Ding,Li Chuzhong,Gui Songbai,Wang Hongyun,Zhang Yazhuo
This study explored the function of microRNAs (miRNAs) in invasive pituitary adenomas (IPA), and developed a microRNA-exosome strategy for the disease treatment. Differentially expressed miRNAs and tumor-associated markers in IPA, non-invasive pituitary adenoma (NIPA), and rat pituitary adenoma cells were identified by bioinformatics analysis and qRT-PCR. Then, the cells were treated by miR-149-5p and miR-99a-3p mimics or inhibitors, or incubated with modified exosome with overexpressed or silenced miRNAs. The cell behaviors were analyzed by molecular experiments. Xenograft assays were constructed by injection of pituitary adenoma cells and exosome into NU/NU nude mice. Tumor size, weight, and expressions of markers related to miRNAs and angiogenesis were determined. Target genes for miR-99a-3p and miR-149 were predicted and verified by bioinformatics analysis and molecular experiments. Twenty differentially expressed miRNAs were identified, among which miR-99a-3p and miR-149 were inhibited in both pituitary adenoma cells and tissues significantly. Expressions of E-cadherin and p53 were down-regulated, while those of MMP-2, MMP-9, N-cadherin, Vimentin, and VEGF were up-regulated in pituitary adenoma cells and tissues, especially in IPA. Further experiments revealed that overexpressed miR-149 and miR-99a-3p inhibited the growth and metastasis of pituitary adenoma cells and tube formation of endothelial cells. MiR-149 and miR-99a-3p overexpressed by exosome showed similar suppressive effects on cell viability, metastasis, tube formation ability, in vivo tumor growth, and expressions of angiogenesis-related markers . Further analysis showed that NOVA1, DTL, and RAB27B were targeted by miR-99a-3p. This study found that overexpressed miR-149-5p and miR-99a-3p induced by exosome could suppress the progression of IPA. Graphical abstract and graphical headlights
1. MiR-149-5p and miR-99a-3p affect the expression of EMT- and ECM-related markers and tumor-related genes in rat pituitary adenoma cells treated with exosomes. 2. Exosome inhibited the tumor growth. 3. Overexpressed miR-149-5p and miR-99a-3p induced by exosome
研究领域:
肿瘤学
·
分子生物学
·
内分泌学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR AND CELLULAR BIOCHEMISTRY
·
2020
·Vol. 476
·期 2
·513-523
·
IF 2.795
Shan Shuhua,Lu Yang,Zhang Xiaoli,Shi Jiangying,Li Hanqing,Li Zhuoyu
Nature polyphenols widely present in plants and foods are promising candidates in cancer chemotherapy. Emerging evidence has shown that plant polyphenols regulate the expression of miRNAs to exert the anti-Multidrug resistance (MDR) activity, which partly attributes to their regulation on miRNAs methylation. Our previous study found that bound polyphenol from foxtail millet bran (BPIS) had potential as an anti-MDR agent for colorectal cancer (CRC), but its mechanism remains unclear. The present findings demonstrated that BPIS upregulated the expression of miR-149 by reducing the methylation of its CpG islands, which subsequently induced the cell cycle arrest in G2/M phase, resulting in enhancing the chemo-sensitivity of HCT-8/Fu cells. Mechanically, BPIS and its active components (FA and p-CA) reduced miR-149 methylation by inhibiting the expression levels of DNA methyltransferases, promoting a remarkable increase of miR-149 expression. Further, the increased miR-149 induced cell cycle arrest in G 2 /M phase by inhibiting the expression of Akt, Cyclin B1 and CDK1, thus increasing the chemosensitivity of HCT-8/Fu cells. Additionally, a strong inducer of DNA de-methylation (5-aza-dc) treatment markedly increased the chemosensitivity of CRC through elevating miR-149 expression, which indicates the hypermethylation of miR-149 may be the key cause of drug resistance in CRC. The study indicates that the enhanced chemosensitivity of BPIS on CRC is mainly attributed to the increase of miR-149 expression induced by methylation inhibition.
研究领域:
肿瘤学
·
药理学
·
分子生物学
·
表观遗传学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
POLYMERS FOR ADVANCED TECHNOLOGIES
·
2025
·Vol. 36
·期 3
·e70136
·
IF 3.4
Ping Xie,Jing He,Yangjun Ou
Photothermal therapy is a promising adjunctive treatment technique requiring a nanoplatform with excellent biocompatibility, photothermal stability, and precise targeting capabilities. This study aims to develop such a nanoplatform by synthesizing two new manganese(II)-based coordination polymers. The polymers were created by integrating 1,4-bis(imidazol-1-yl)benzene with the ternary ligand tris( p -carboxyphenyl)phosphane oxide, resulting in the formulas {[Mn 3 (L) 2 (bib) 3 (H 2 O) 7 ]·12H 2 O} n (CP 1 ) and {[Mn(HL)(bib)]·H 2 O} n (CP 2 ). These structures, with large surface areas and porosity, enhance drug loading efficiency. Doxorubicin (DOX) was successfully incorporated into a biocompatible HA/CMCS hydrogel-CP composite (HA/CMCS-CPs@DOX), forming a robust nanotherapeutic platform. Under near-infrared light irradiation, these metal-hydrogel composites effectively induced localized hyperthermia, aiding ocular melanoma treatment. We evaluated the effect of HA/CMCS-CP 2 @DOX on the cell proliferation of the uveal melanoma cell line, and the regulatory effects of the system on lncRNA ARAP1-AS1/miR-149-3p/S100A4 were also explored.
研究领域:
材料科学
·
癌症治疗
·
药物递送系统
·
分子生物学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2025
·
IF 5.4
Junjie Liu,Jingjing Liu,Yuxin Qiao,Hanxin Zhong,Jiaoxia Wei,Dongyang Han,Jin Peng,Yongzhou Feng,Danni Wang,Yujie Cheng,Haitao Lu,Li Yao
Ethnopharmacological relevance We previous study verified that decadienyl-L-carnitine (C10:2) biosynthesis has therapeutic-target capacity for RCE inhibiting pulmonary vascular remodeling to modulate experimental pulmonary hypertension(PH). However, the profound molecular mechanism remains incompletely elucidated. Aim of study This study aim to investigate whether C10:2 biosynthesis regulates pulmonary vascular remodeling by activating cell pyroptosis. Materials and methods Rats and pulmonary artery smooth musle cells (PASMCs) model with PH were successfully induced with monocrataline (MCT) and platelet-derived growth factor-BB (PDGF-BB) in present study. Following RCE treatment, cell targeted metabolomics assay combining biological information analysis and molecular biological methods were used to investigate the modulatory function of C10:2 on pulmonary vascular remodeling by activating cell pyroptosis and accordingly pharmacological mechanism of RCE against cell pyroptosis. Results We found that C10:2 activated NLRP3/Caspase-1/GSDMD signaling pathway to promote PASMCs pyroptosis, and decreased the level of azelaic acid in PASMCs. RCE can significantly upregulate miR-149-5p to targeting bind Cpt1a mRNA, thus, to decrease CPT1A expression, by which low level of C10:2 was maintained to further promote the biosynthesis of anti-inflammatory azelaic acid in vivo, along with this functional molecule is also one main compound of RCE. Our data further demonstrated that the biosynthesis of azelaic acid directly regulates NLRP3/Caspase1/GSDMD axis to inhibit pyroptosis by targeting NLRP3, we therefore argue that azelaic acid is a key functional compound of RCE for treating PH by inhibiting cell pyroptosis. Conclusion Collectively, our work characterized that azelaic acid is a key functional compound in RCE to express pharmacological efficacy against PH, which was observed to inhibit cell pyroptosis to ameliorate pulmonary vascular remodeling in rats through the regulation of decadienyl-L-carnitine/NLRP3/GSDMD axis. Such work will provide essentially molecular basis for developing anti-PH strategy and associated drug discovery.
研究领域:
药理学
·
分子生物学
·
心血管研究
·
民族药理学
·
代谢组学
·
细胞生物学
✓ 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）