SPOP downregulation promotes bladder cancer progression based on cancer cell-macrophage crosstalk via STAT3/CCL2/IL-6 axis and is regulated by VEZF1
Meiqian LiYangyan CuiQi QiJiakuan LiuJiaxuan LiGuifang HuangJiale YangJingya SunZhihui MaShengjie LiangDianzheng ZhangJun JiangRujian ZhuQiuli LiuRuimin HuangJun Yan
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Abstract:
Cancer cells are intimately intertwined with tumor microenvironment (TME), fostering a symbiotic relationship propelling cancer progression. However, the interaction between cancer cells and tumor-associated macrophages (TAMs) in urothelial bladder cancer (UBC) remains poorly understood.Keywords:
Crosstalk
Most of advanced hypopharyngeal squamous cell carcinoma (HSCC) are resistant to chemotherapy, and there is still lack of effective treatment for HSCC now. The present study aimed to investigate whether downregulation of RNA-binding motif protein 17 (RBM17) could enhance cisplatin sensitivity and inhibit cell invasion in HSCC and the underlying mechanism. We observed that RBM17 was upregulated in tumor tissues and associated with poor progression. Treatment of FaDu cells with cisplatin increased RBM17 expression in mRNA levels. Downregulation of RBM17 enhanced cisplatin-mediated inhibition of FaDu cells. In addition, downregulation of RBM17 effectively suppressed tumor cell migration and invasion through the reversion of epithelial-mesenchymal transition. Moreover, downregulation of RBM17 could significantly slow tumor growth in FaDu xenograft tumor model. Liquid chromatography-mass spectrometry/mass spectrometry detection and independent PRM analysis showed that 21 differentially expressed proteins were associated with the downregulation of RBM17. Taken together, our study implied that downregulation of RBM17 could serve as a novel approach to enhance cisplatin sensitivity in HSCC.
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significantly increased in cells along with the upregulation of GPR65 (Fig. 5C,D)", it previously said "Transcriptome, qPCR, and WB results revealed that the expression levels of MYLK and MYLK3 were significantly decreased in cells along with the upregulation of GPR65 (Fig. 5C, D)".
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Two Ca 2+ ‐activated Cl − currents ( I Cl(Ca) ) are present in vascular smooth muscle (VSMC). One is cGMP dependent, the other is characterized as a classical I Cl(Ca) . Here we downregulate bestrophin‐3 (best3) and TMEM16A, to assess their importance for the two I Cl(Ca) and for the role of I Cl(Ca) in vascular function. Best3 and TMEM16A were downregulated in rat small mesenteric arteries using siRNA. Knockdown was confirmed at mRNA and protein levels 3 days after transfection. Best3 downregulation suppressed the cGMP‐dependent I Cl(Ca) while TMEM16A downregulation suppresed both I Cl(Ca) s. Both best3 and TMEM16A downregulation suppressed oscillations in vascular tone i.e. vasomotion. Best3 downregulation was without effect on sensitivity and maximal force production to norepinephrine while TMEM16A downregulation significantly reduced both. Also the force production to 125 mM KCl was reduced by TMEM16A downregulation. We conclude that TMEM16A is essential for both I Cl(Ca) s while best3 may be modifying the TMEM16A current characteristics in a subset of channels. The cGMP‐dependent I Cl(Ca) is critical for vasomotion and normal expression of TMEM16 is essential for VSMC conctractility.
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Mesenteric arteries
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Maternal viral infection is known to increase the risk for schizophrenia and autism in their offspring (Brown et al, 2004). C57BL/6 mice were infected with human influenza virus on day E18 of pregnancy and brains were collected at PN days 0, 14, or 56, from virally-exposed (N=3) or sham-infected control's (N=3) offspring. Microarray analysis of virally-exposed mouse brains showed significant (p<0.05) upregulation of 15 genes and downregulation of 3 genes in cerebellum, upregulation of 42 genes and downregulation of 9 genes in hippocampus, and upregulation of 4 genes and downregulation of 5 genes in prefrontal cortex vs. controls in day 0 mice. At day 14, there was a significant upregulation of 2 genes and downregulation of 0 genes in cerebellum, upregulation of 1 gene and downregulation of 1 gene in hippocampus, and upregulation of 3 genes and downregulation of 3 genes in prefrontal cortex vs. controls. At day 56, there was a significant upregulation of 13 genes and downregulation of 2 genes in cerebellum, upregulation of 4 genes and downregulation of 3 genes in hippocampus, and upregulation of 4 genes and downregulation of 1 gene in prefrontal cortex vs. controls. Implications of changes in brain genes for development of abnormal brain structure and function will be discussed. The generous support by the National Institute for Child Health and Human Development (1-R01-HD046589-01A2) to S.H.F. is greatly appreciated.
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Li, Xiaoyan; Wang, Xiaofang; Jiang, Li; Harris, Peter C.; Li, Xiaogang; Torres, Vicente E. Author Information
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Cancer cells differ from normal cells in both gain of functions (i.e., upregulation) and loss of functions (i.e., downregulation). While it is common to suppress gain of function for chemotherapy, it remains challenging to target downregulation in cancer cells. Here we show the combination of enzyme-instructed assembly and disassembly to target downregulation in cancer cells by designing peptidic precursors as the substrates of both carboxylesterases (CESs) and alkaline phosphatases (ALPs). The precursors turn into self-assembling molecules to form nanofibrils upon dephosphorylation by ALP, but CES-catalyzed cleavage of the ester bond on the molecules results in disassembly of the nanofibrils. The precursors selectively inhibit the cancer cells that downregulate CES (e.g., OVSAHO) but are innocuous to a hepatocyte that overexpresses CES (HepG2), while the two cell lines exhibit comparable ALP activities. This work illustrates a potential approach for the development of chemotherapy via targeting downregulation (or loss of functions) in cancer cells.
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"Downregulation of miR-140-3p Is a Cause of Upregulation of RhoA Protein in Bronchial Smooth Muscle of Murine Experimental Asthma." American Journal of Respiratory Cell and Molecular Biology, 64(1), pp. 138–140
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