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991.
992.
Rui Bai Cheng Yuan Wenjie Sun Jianguo Zhang Yuan Luo Yanping Gao Yangyi Li Yan Gong Conghua Xie 《International journal of biological sciences》2021,17(8):1995
Abnormal expression and dysfunction of Never-in-mitosis-A-related kinase 2 (NEK2) result in tumorigenesis. High levels of NEK2 are related to malignant progression, drug resistance, and poor prognosis. However, the relationship between NEK2 levels and the occurrence of non-small cell lung cancer (NSCLC) remains unknown. This study aimed to explore the impacts of NEK2 on the oncogenesis of NSCLC and the tumor microenvironment. Downregulation of NEK2 inhibited A549 and H1299 cell proliferation, migration, and invasion, blocking cell cycle at the G0/G1 phase. Loss of NEK2 inhibited the release of IL-10 from tumor cells, M2-like polarization of macrophages, angiogenesis, and vascular endothelial cell migration. Furthermore, NEK2 deficiency inhibited tumor growth in vivo. Taken together, NEK2 knockdown inhibited the occurrence and development of NSCLC, M2 polarization of macrophages, and angiogenesis. The abnormal expression of NEK2 might not only indicate tumor progression and patient prognosis but also serve as a potential molecular therapeutic target with great development prospects. 相似文献
993.
Yaomin Luo Xintong Lu Wenrong Ma Yang Xiao Chen Wei Xiaoxia Yuan Yueyue Wu Yunlin Wang Yiman Xiong Xin Yu Xue Wu Siqi He Yayudie Liu Jinjing Wang Qing Wu Hui Zhou Zhen Jiang 《Journal of cellular and molecular medicine》2023,27(22):3591-3600
Long non-coding RNAs (lncRNA) have an extensive role in the progression and chemoresistance of gastric cancer (GC). Deeply study the regulatory role of lncRNAs could provide potential therapeutic targets. The aim of this study is to explore the regulatory role of HOTAIR in the progression and oxaliplatin resistance of GC. The expression of HOTAIR in GC and cell lines were detected by using qRT-PCR. Cell proliferation and apoptosis were analysed by CCK-8, EdU incorporation and flow cytometry. Luciferase reporter assay was used to identify the interaction between HOTAIR and ABCG2 (ATP-binding cassette (ABC) superfamily G member 2, ABCG2) via miR-195-5p. The regulatory functions were verified by using molecular biology experiments. HOTAIR was significantly overexpressed in GC and associated with poor prognosis. Knock-down of HOTAIR inhibited the GC cells proliferation and oxaliplatin resistance, while overexpression of HOTAIR showed opposite functions. Further studies found that HOTAIR acted as a competing endogenous RNA (ceRNA) to absorb miR-195-5p and elevated the expression of ABCG2, which leads to resistance of GC cells to oxaliplatin. Taken together, our findings demonstrated that HOTAIR regulates ABCG2 induced resistance of GC to oxaliplatin through miR-195-5p signalling and illustrate the great potential of developing new therapeutic targets for GC patients. 相似文献
994.
Fei Zhao Weiwei Huang Tamgue Ousman Bin Zhang Yangyang Han Daguia Zambe John Clotaire Chen Wang Huanhuan Chang Huanan Luo Xiaoyong Ren Ming Lei 《PloS one》2013,8(11)
Triptolide, an active compound extracted from Chinese herb Leigongteng (Tripterygium wilfordii Hook F.), shows a broad-spectrum of anticancer activity through its cytotoxicity. However, the efficacy of triptolide on laryngocarcinoma rarely been evaluated, and the mechanism by which triptolide-induced cellular apoptosis is still not well understood. In this study, we found that triptolide significantly inhibited the laryngocarcinoma HEp-2 cells proliferation, migration and survivability. Triptolide induces HEp-2 cell cycle arrest at the G1 phase and apoptosis through intrinsic and extrinsic pathways since both caspase-8 and -9 are activated. Moreover, triptolide enhances p53 expression by increasing its stability via down-regulation of E6 and E6AP. Increased p53 transactivates down-stream target genes to initiate apoptosis. In addition, we found that short time treatment with triptolide induced DNA damage, which was consistent with the increase in p53. Furthermore, the cytotoxicity of triptolide is decreased by p53 knockdown or use of caspases inhibitor. In conclusion, our results demonstrated that triptolide inhibits cell proliferation and induces apoptosis in laryngocarcinoma cells by enhancing p53 expression and activating p53 functions through induction of DNA damage and suppression of E6 mediated p53 degradation. These studies indicate that triptolide is a potential anti-laryngocarcinoma drug. 相似文献
995.
996.
Guo C Liu K Zheng Y Luo H Chen H Huang L 《Apoptosis : an international journal on programmed cell death》2011,16(6):606-618
Human papilloma virus type 16 (HPV16) E7 is a viral oncoprotein that is believed to play a major role in cervical neoplasia.
A novel antagonist peptide against HPV16 E7 was previously selected by phage display screening and the selected peptide was
found to have anti-tumor efficacy against HPV16-positive cervical carcinoma through induction of cell cycle arrest. In the
current study, to further elucidate the mechanisms of the antagonist peptide, the effects of the peptide on apoptosis are
investigated by RT-PCR, Western blotting, MTT assay, TUNEL staining, Annexin V apoptosis assay, flow cytometry, and animal
experiments. The antagonist peptide showed obvious anti-tumor efficacy through apoptosis induction, both in HPV16-positive
cervical cancer cell lines and tumor xenografts. Our results also revealed that the peptide induced accumulation of cellular
p53 and p21, and led to HPV16 E7 protein degradation. In the case of mRNA levels, it resulted in unaltered p53 and HPV16 E7
expression, but increased expression of p21. In contrast, the induction of apoptosis and p53 reactivation effects by the selected
peptide were abolished after E7 knocked down with siRNA. These results demonstrate that the selected peptide can induce E7
degradation and lead to marked apoptosis in HPV16-related cancer cells by activating cellular p53 and its target genes, such
as p21. Furthermore, the evident therapeutic efficacy obtained from the subcutaneous tumor model experiments in nude mice
suggests a therapeutic potential for HPV16-related cancers of the selected peptide. Therefore, this specific peptide may be
used to create specific biotherapies for the treatment of HPV 16-positive cervical cancers. 相似文献
997.
Wenping Luo Zhenzhen Liu Dongmei Tan Qian Zhang Hongying Peng Yingxiong Wang Yi Tan 《Molecular reproduction and development》2013,80(1):59-69
Uterine decidualization, characterized by stromal cell proliferation and differentiation into polyploid decidual cells, is critical to the establishment of pregnancy in mice, although the mechanism underlying this process remains poorly understood. This study is the first to investigate the expression of gamma‐amino butyric acid (GABA) and the GABA A‐type receptor π subunit (GABPR) in the early‐pregnancy mouse uterus and their roles in decidualization. The expression of GABRP was detected from Day 4 to 8 of pregnancy. The effects of GABA and GABA A‐type receptor on cell proliferation and apoptosis were investigated using the Cell Titer 96® AQueous One Solution Cell Proliferation Assay and flow cytometry. The levels of cyclin D3 protein were measured in cultured stromal cells artificially induced to undergo decidualization, and treated with GABA and a GABA A‐type receptor agonist or antagonist, respectively, at the same time. mRNA expression of gabrp in implantation sites was lower than that in inter‐implanted sites. GABA and GABRP protein were localized in the luminal and glandular epithelium, stromal cells, and decidual cells. In vitro, GABPR protein level was decreased in cultured stromal cells during the decidualization process. The addition of GABA and the GABA A‐type receptor agonist Muscimol inhibited stromal cell proliferation, promoted apoptosis, and arrested cells in S‐phase, followed by decreased expression of cyclin D3. These results show that in mice, GABA was actively involved in inhibiting stromal cell proliferation and suppresses decidualization progress through GABA A‐type receptors by down‐regulating cyclin D3 level. Mol. Reprod. Dev. 80: 59–69, 2013. © 2012 Wiley Periodicals, Inc. 相似文献
998.
999.
1000.
Chun‐Hsiang Huang Tzu‐Ping Ko Chun‐Chi Chen Hsiu‐Chien Chan Ya‐Shan Cheng Zhen Zhu Juergen Wiegel Wenhua Luo Rey‐Ting Guo Yanhe Ma 《Proteins》2013,81(7):1256-1265
Xylanases are capable of decomposing xylans, the major components in plant cell wall, and releasing the constituent sugars for further applications. Because xylanase is widely used in various manufacturing processes, high specific activity, and thermostability are desirable. Here, the wild‐type and mutant (E146A and E251A) catalytic domain of xylanase from Thermoanaerobacterium saccharolyticum JW/SL‐YS485 (TsXylA) were expressed in Escherichia coli and purified subsequently. The recombinant protein showed optimal temperature and pH of 75°C and 6.5, respectively, and it remained fully active even after heat treatment at 75°C for 1 h. Furthermore, the crystal structures of apo‐form wild‐type TsXylA and the xylobiose‐, xylotriose‐, and xylotetraose‐bound E146A and E251A mutants were solved by X‐ray diffraction to high resolution (1.32–1.66 Å). The protein forms a classic (β/α)8 folding of typical GH10 xylanases. The ligands in substrate‐binding groove as well as the interactions between sugars and active‐site residues were clearly elucidated by analyzing the complex structures. According to the structural analyses, TsXylA utilizes a double displacement catalytic machinery to carry out the enzymatic reactions. In conclusion, TsXylA is effective under industrially favored conditions, and our findings provide fundamental knowledge which may contribute to further enhancement of the enzyme performance through molecular engineering. Proteins 2013; 81:1256–1265. © 2013 Wiley Periodicals, Inc. 相似文献