scholarly journals N2-neutrophils Promote Invasion and Metastasis of Ovarian Cancer by Upregulating MAPK Signaling

2020 ◽  
Author(s):  
caixia li ◽  
Chuandi Men ◽  
Weihong Yang ◽  
Qi Liu ◽  
Shupeng Liu ◽  
...  

Abstract Background: Metastasis is an important factor of high mortality in ovarian cancer. Neutrophils are involved in multiple pathologic mechanisms of cancer,including invasion and metastasis. However, the relationship of neutrophils and invasion and metastasis in ovarian cancer is unclear,as well as the exact mechanism.Methods:To verify the relationship of neutrophils and invasion and metastasis in ovarian cancer,we tested the expression of CD11b in 24 groups of benign and malignant ovarian tumor tissues.And then,we tested the expression of CD11b,CXCL8,and CXCR1 in 16 cases of ovarian cancer,including primary lesions, metastatic lesions and adjacent carcinoma tissues.We successfully build tumor associated neutrophils research model (N1 and N2) and prove that N2-neutrophils can promote the invasion and metastasis of ovarian cancer. Next,we screened the significantly changed MAPK signaling pathway by high-throughput sequencing. And then confirmed this conclusion by molecular biology experiments. Results:The expression of CD11b was significantly higher in malignant tumor than benign tumor tissues tested by western blot and Immunohistochemistry.The expression of CD11b,CXCL8 and CXCR1 is highest in ovarian cancermetastases ,followed by the primary lessions, and then the adjacent carcinoma tissues tested by PCR and WB methods.We proved that N2-neutrophils can promote the invasion and metastasis of ovarian cancer by transwell assay.Forthermore,we detected the related indicators of metastasis including MMP-2,MMP-9,E-Cadherin,N-cadherin and Vimentin by PCR and WB methods.Next,we screened the significantly changed MAPK signaling pathway by High-throughput sequencing through comparing ovarian cancer cells before and after co-cultured with N2-neutrophils. At last,we found the key gene P38 of MAPK signaling pathway by molecular biology experiments. Conclusions: N2-neutrophils promote the invasion and metastasis of ovarian cancer by Upregulating MAPK signaling pathway, find a key gene P38.

2016 ◽  
Vol 48 (7) ◽  
pp. 455-463 ◽  
Author(s):  
Jing Yu ◽  
Ke He ◽  
Ting Ren ◽  
Yaping Lou ◽  
Ayong Zhao

Broodiness is the primary factor influencing egg production in geese, in which several genes and miRNAs participate. Detailed spatiotemporal profiles of miRNAs encompassing follicle development levels, however, are lacking. In this study, we collected preovulatory follicles (classified as small white follicles, large white follicles, and small yellow follicles) from brooding and laying geese and aimed to analyze microRNA (miRNA or miR) during folliculogenesis. High-throughput sequencing and bioinformatics analysis were used to identify the miRNAs involved in follicle development. The let7 family, miR-10 family, and miR-143 family were abundant in these libraries, and they have been suggested to play a housekeeping role during folliculogenesis. Joint comparisons revealed 23 upregulated and 21 downregulated miRNAs (in at least two comparisons of follicles during brooding and laying, P < 0.1) in the laying stage. Unlike reproduction pathways reported for ovaries, GO and KEGG analysis suggested pathways for cell apoptosis and proliferation, such as the regulation of actin cytoskeleton, endocytosis, axon guidance, pathways in cancer, tight junctions, focal adhesion, the MAPK signaling pathway, cytokine-cytokine receptor interactions, and the Wnt signaling pathway in folliculogenesis. This study revealed the miRNAs that were directly involved in follicular atresia, and our results added to the understanding of the functional involvement of miRNAs during specific stages of follicle development.


2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Li-qian Zhang ◽  
Rong-wei Lv ◽  
Xiang-dong Qu ◽  
Xian-jun Chen ◽  
Hong-sheng Lu ◽  
...  

Aloesin is an active constituent of the herb aloe vera and plays a crucial role in anti-inflammatory activity, ultraviolet protection, and antibacterium. We investigated the role and possible mechanisms of aloesin in the cell growth and metastasis of ovarian cancer. It was found that aloesin inhibited cell viability and cell clonality in a dose-dependent manner. It arrests the cell cycle at the S-phase and induced apoptosis in SKOV3 cells. In an in vivo experiment, it was observed that aloesin inhibited tumor growth. Moreover, it inhibited migration and invasion of cancer in SKOV3 cells. Interestingly, members from the mitogen-activated protein kinase (MAPK) signaling family became less phosphorylated as the aloesin dose increased. This suggests that aloesin exerts its anticancer effect through the MAPK signaling pathway. Our data also highlights the possibility of using aloesin as a novel therapeutic drug for ovarian cancer treatment.


2021 ◽  
Author(s):  
Mingmin he ◽  
Xiongwei Cai ◽  
Yuanyuan Zeng

Abstract The purpose of this study was to investigate the relationship between RUNX1 mutations and MAPK signaling pathway in acute myeloid leukemia (AML). In this study, we analyzed miRNA expression with 5 mutant RUNX1 and 9 wild-type RUNX1 cases from TCGA database of AML. Six miRNAs were differently expressed with significance, and three of them were related to overall survival. Predicted target genes of these 3 miRNAs were highly enriched in MAPK signaling pathway by functional enrichment with miRWalk3.0. Besides, genes among RUNX1 associated genes directly regulated by RUNX1 were involved in MAPK signaling pathway, too. Taken together, we demonstrate three DEmiRNAs and three genes correlated to RUNX1 were correlated with prognosis in AML, and RUNX1 modulated MAPK signaling pathway in AML.


2018 ◽  
Vol 315 (2) ◽  
pp. C225-C235 ◽  
Author(s):  
Ying Chen ◽  
Xiao-Yun Cao ◽  
Ying-Ni Li ◽  
Yu-Yan Qiu ◽  
Ying-Na Li ◽  
...  

Some microRNAs (miRs) are dysregulated in cancers, and aberrant miR expression has been reported to correlate with chemoresistance of cancer cells. Therefore, the present study aims at investigating the effects of microRNA-139-5p (miR-139-5p) on cisplatin resistance of ovarian cancer (OC) with involvement of ring finger protein 2 (RNF2) and the mitogen-activated protein kinase (MAPK) signaling pathway. OC tissues were obtained from 66 primary OC patients. The cisplatin-sensitive A2780 and cisplatin-resistant A2780/DDP cell lines were collected for construction of RNF2 silencing and overexpressed plasmids. Cell vitality and apoptosis were detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and annexin V-FITC/propidium iodide double-staining, respectively. Next, expression of RNF2, extracellular signal-related kinase, and p38 was determined by quantitative reverse transcription-quantitative polymerase chain reaction and Western blot analysis. Finally, the volume of xenograft tumors in BALB/c nude mice was detected. RNF2 and miR-139-5p were identified to be involved in OC. In addition, MAPK activation and RNF2 were related to cisplatin resistance of OC. miR-139-5p was downregulated in cisplatin-resistant OC tissues, and miR-139-5p overexpression could inhibit cell vitality, reduce cisplatin resistance, and promote apoptosis of OC cells. Furthermore, miR-139-5p combined with MAPK inhibitors more obviously reduced cisplatin resistance of OC. Taken together, this study demonstrated that miR-139-5p overexpression combined with inactivation of the MAPK signaling pathway can reverse the cisplatin resistance of OC by suppressing RNF2. Thus, miR-139-5p overexpression might be a future therapeutic strategy for OC.


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