stat3 pathway
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Author(s):  
Zhengru Liu ◽  
Mingming Qi ◽  
Shan Tian ◽  
Qian Yang ◽  
Jian Liu ◽  
...  

Ubiquitin-specific protease 25 (USP25) plays an important role in inflammation and immunity. However, the role of USP25 in acute pancreatitis (AP) is still unclear. To evaluate the role of USP25 in AP, we conducted research on clinical AP patients, USP25wild-type(WT)/USP25 knockout (USP25−/−) mice, and pancreatic acinar cells. Our results showed that serum USP25 concentration was higher in AP patients than in healthy controls and was positively correlated with disease severity. AP patients’ serum USP25 levels after treatment were significantly lower than that at the onset of AP. Moreover, USP25 expression was upregulated in cerulein-induced AP in mice, while USP25 deficiency attenuates AP and AP-related multiple organ injury. In vivo and in vitro studies showed that USP25 exacerbates AP by promoting the release of pro-inflammatory factors and destroying tight junctions of the pancreas. We showed that USP25 aggravates AP and AP-related multiple organ injury by activating the signal transducer and activator of transcription 3 (STAT3) pathway. Targeting the action of USP25 may present a potential therapeutic option for treating AP.


2022 ◽  
Vol 11 ◽  
Author(s):  
Jingjing Ma ◽  
Qiong Shi ◽  
Sen Guo ◽  
Peng Xu ◽  
Xiuli Yi ◽  
...  

Melanoma is the most lethal skin cancer that originates from epidermal melanocytes. Recently, long non-coding RNAs (lncRNAs) are emerging as critical regulators of cancer pathogenesis and potential therapeutic targets. However, the expression profile of lncRNAs and their role in melanoma progression have not been thoroughly investigated. Herein, we firstly obtained the expression profile of lncRNAs in primary melanomas using microarray analysis and unveiled the differentially-expressed lncRNAs compared with nevus. Subsequently, a series of bioinformatics analysis showed the great involvement of dysregulated lncRNAs in melanoma biology and immune response. Further, we identified lncRNA CD27-AS1-208 as a novel nuclear-localized factor with prominent facilitative role in melanoma cell proliferation, invasion and migration. Mechanistically, CD27-AS1-208 could directly interact with STAT3 and contribute to melanoma progression in a STAT3-dependent manner. Ultimately, the role of CD27-AS1-208 in melanoma progression in vivo was also investigated. Collectively, the present study offers us a new horizon to better understand the role of lncRNAs in melanoma pathogenesis and demonstrates that CD27-AS1-208 up-regulation contributes to melanoma progression by activating STAT3 pathway. Targeting CD27-AS1-208 in melanoma cells can be exploited as a potential therapeutic approach that needs forward validation in clinical trials in the future.


Author(s):  
Yuanhe You ◽  
Zhuowei Tian ◽  
Zhong Du ◽  
Kailiu Wu ◽  
Guisong Xu ◽  
...  

Abstract Background Tumor-associated macrophages (TAMs) have a leading position in the tumor microenvironment. Previously, we have demonstrated that M1-like TAMs activated by exosome-transferred THBS1 promote malignant migration in oral squamous cell carcinoma (OSCC). However, the functional roles and associated molecular mechanisms of the activated M1-like TAMs need to be further clarified in OSCC. Methods Conditioned Media (CM) were harvested from the exosome activated M1-like TAMs. We measured the malignant behaviors of OSCC under the treatment of CM from M1-like TAMs by performing colony forming assays, invasion assays, wound-healing assays, spheroid forming assays and in vivo xenograft experiments. The underlying mechanisms were investigated by RNA-seq, cytokines analysis, intracellular signaling pathway analysis, ChIP assays, bioinformatics analysis and validation. Results M1-like TAMs significantly promoted the epithelial-mesenchymal transition (EMT) process, and induced the cancer-stem like cells (CSCs) by upregulating the expression of MME and MMP14 in OSCC cells. Cytokine analysis revealed a shark increase of IL6 secretion from M1-like TAMs. Blocking IL6 in the CM from M1-like TAMs could significantly weaken its effects on the colony forming, invasion, migration, microsphere forming and xenograft forming abilities of OSCC cells. Cellular signaling assays indicated the activation of Jak/Stat3 pathway in the OSCC cells treated by the CM from M1-like TAMs. Blocking the activation of the Jak/Stat3 pathway could significantly weaken the effects of M1-like TAMs on the colony forming, invasion, migration, microsphere forming and xenograft forming abilities of OSCC cells. Further RNA-seq analysis and bioinformatics analysis revealed an increased expression of THBS1 in the OSCC cells treated by M1-like TAMs. Bioinformatics prediction and ChIP assays revealed the activation of Stat3 by CM from M1-like TAMs could directly promote the transcription of THBS1 in OSCC cells. Conclusions We proposed that M1-like TAMs could cascade a mesenchymal/stem-like phenotype of OSCC via the IL6/Stat3/THBS1 feedback loop. A better understanding on the functional roles and associated molecular mechanisms of M1-like TAMs might facilitate the development of novel therapies for supplementing the current treatment strategies for OSCC patients.


2022 ◽  
pp. 303-317
Author(s):  
Ruifan Wu ◽  
Xinxia Wang
Keyword(s):  

BIOCELL ◽  
2022 ◽  
Vol 46 (3) ◽  
pp. 689-697
Author(s):  
SHUTING GU ◽  
JINGYI QIN ◽  
SAINAN GAO ◽  
ZHEN WANG ◽  
QI MENG ◽  
...  

BIOCELL ◽  
2022 ◽  
Vol 46 (5) ◽  
pp. 1319-1328
Author(s):  
YANG YANG ◽  
LIJUAN FU ◽  
CHUNMEI CHEN ◽  
MEIWEI HU

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