scholarly journals The interplay among MAP3K1 and SOX2 regulated metastasis by MAPK signaling pathway through interaction with KLF4 in triple-negative breast cancer

2021 ◽  
Author(s):  
Lixiang Zheng ◽  
Xilei Zheng ◽  
Xiaoying Ren ◽  
Ping Hunag ◽  
Ke Wang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Triple Negative ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Expression Level ◽  
Cause Of Deaths ◽  
Proliferation And Metastasis ◽  
Cell Proliferation And Metastasis

Abstract BackgroundTumor metastasis with poor prognosis is still the leading cause of deaths among triple-negative breast caner (TNBC) patients. Therefore, understanding the underlying molecular mechanisms of TNBC metastasis and identifying the molecules contributing to the process are of great importance.It would be provided targets for the prevention and treatment of recurrence and metastasis of TNBC. MethodsThe expression level of MAP3K1 and its up-or downstream genes,SOX2 and KLF4 were detected using Western blotting assay. Cell migration and proliferation were measure by xCELLigence Real-Time Cell Analyzer (RTCA). Protein interaction was used for co-immunorecipitation. ResultCompared with metastasis (Met) in TBNC model, the expression of MAP3K1,KLF4,ERK1/2, C-jun and werelower, while SOX2, Ras,Rafand c-Fos were higher in non-metastasis (non-Met) samples. In MAP3K1 silenced MDA-MB-231 cells, the cell proliferation and metastasis rates were increased. The expression level of KLF4 was lower than SOX2 reduced or minimal interaction of both. In SOX2 silenced MDA-MB-231 cells, the cell proliferation and metastasis rates were decreased, while the expression of KLF4 and MAP3K1 were higher, the interaction of MAP3K1 and KLF4 was inhibited. ConclusionsIt is demonstrated for the very first time that SOX2 and MAP3K1 are playing an important rolesin TNBC cell metastasis by regulating MAPK signaling pathway by interacting with KLF4 .

scholarly journals miR-3188 Regulates Cell Proliferation, Apoptosis, and Migration in Breast Cancer by Targeting TUSC5 and Regulating the p38 MAPK Signaling Pathway

2018 ◽  
Vol 26 (3) ◽  
pp. 363-372 ◽  
Author(s):  
Xiaowen Chen ◽  
Jianli Chen
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Signaling Pathway ◽  
P38 Mapk ◽  
Molecular Mechanisms ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Luciferase Reporter ◽  
And Migration ◽  
Mcf 7

This study intended to investigate the effects of miR-3188 on breast cancer and to reveal the possible molecular mechanisms. miR-3188 was upregulated and TUSC5 was downregulated in breast cancer tissues and MCF-7 cells compared to normal tissue and MCF-10 cells. After MCF-7 cells were transfected with miR-3188 inhibitor, cell proliferation and migration were inhibited, whereas apoptosis was promoted. Luciferase reporter assay suggested that TUSC5 was a target gene of miR-3188. In addition, miR-3188 overexpression increased the p-p38 expression, while miR-3188 suppression decreased the p-p38 expression significantly. miR-3188 regulated breast cancer progression via the p38 MAPK signaling pathway. In conclusion, miR-3188 affects breast cancer cell proliferation, apoptosis, and migration by targeting TUSC5 and activating the p38 MAPK signaling pathway. miR-3188 may serve as a potential therapeutic agent for the treatment of breast cancer.

scholarly journals Aldolase A Promotes Proliferation and Metastasis of Colorectal Cancer through Targeting COPS6 and Regulating MAPK Signaling Pathway

2021 ◽  
Author(s):  
Ya Lu ◽  
Yuan Zhang ◽  
Hui Zhang ◽  
Yue Zhu ◽  
Junying Zhang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Signaling Pathway ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Invasion And Migration ◽  
Proliferation And Metastasis ◽  
And Migration ◽  
Aldolase A

Abstract Background: Colorectal cancer (CRC) is a serious threat to human health, and its underlying mechanisms needs further explored. Aldolase A (ALDOA) has received increasing attention for its reported association with multiple cancers, but the function and mechanism of ALDOA in CRC remain unclear. We aimed to evaluate the biological role of ALDOA in CRC.Methods: The stable ALDOA knockdown or overexpression cell lines were established for subsequent experiments. The qRT-PCR and western blotting were used to detect the expression of ALDOA and COPS6 and the relative protein levels of epithelial-mesenchymal transition (EMT) and MAPK signaling pathway. Immunofluorescence (IF) assay was applied to determine ALDOA localization. CCK-8, transwell, and wound healing assays were performed to evaluate CRC cell proliferation, invasion, and migration. Mouse xenograft models were established to verify the effect of ALDOA on CRC cell growth in vivo. Immunoprecipitation (IP) assay and mass spectrometry (MS) analysis were conducted to identify the interactions between ALDOA and COPS6.Results: ALDOA was overexpressed in CRC tissues and cell lines. Silencing ALDOA significantly impaired the proliferation, invasion and migration of CRC cells in vitro, and obviously decreased the growth of CRC cells in vivo. Mechanically, ALDOA bound to and regulated COPS6, and the promoting effects of upregulated ALDOA on CRC cell proliferation and metastasis were inhibited by the depletion of COPS6. Besides, EMT program and MAPK signaling pathway were activated by ALDOA overexpression.Conclusion: ALDOA facilitated the proliferation, invasion and migration of CRC through binding and regulating COPS6, inducing EMT and activating MAPK signaling pathway.

scholarly journals Long noncoding RNA 00976 promotes pancreatic cancer progression through OTUD7B by sponging miR-137 involving EGFR/MAPK pathway

2019 ◽  
Vol 38 (1) ◽  
Author(s):  
Shan Lei ◽  
Zhiwei He ◽  
Tengxiang Chen ◽  
Xingjun Guo ◽  
Zhirui Zeng ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Proliferation ◽  
Signaling Pathway ◽  
Mapk Pathway ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Migration And Invasion ◽  
Potential Biomarker

Abstract Background Accumulation evidence indicates the vital role of long non-coding RNAs (lncRNAs) in tumorigenesis and the progression of malignant tumors, including pancreatic cancer (PC). However, the role and the molecular mechanism of long non-coding RNA 00976 is unclear in pancreatic cancer. Methods In situ hybridization (ISH) and qRT-PCR was performed to investigate the association between linc00976 expression and the clinicopathological characteristics and prognosis of patients with PC. Subsequently, linc00976 over-expression vector and shRNAs were transfected into PC cells to up-regulate or down-regulate linc00976 expression. Loss- and gain-of function assays were performed to investigate the role of linc00976 in proliferation and metastasis in vitro and vivo. ITRAQ, bioinformatic analysis and rescue assay were used to illustrate the ceRNA mechanism network of linc00976/miR-137/OTUD7B and its downstream EGFR/MAPK signaling pathway. Results linc00976 expression was overexpressed in PC tissues and cell lines and was positively associated with poorer survival in patients with PC. Function studies revealed that linc00976 knockdown significantly suppressed cell proliferation, migration and invasion in vivo and in vitro, whereas its overexpression reversed these effects. Based on Itraq results and online database prediction, Ovarian tumor proteases OTUD7B was found as a downstream gene of linc00976, which deubiquitinated EGFR mediates MAPK signaling activation. Furthermore, Bioinformatics analysis and luciferase assays and rescue experiments revealed that linc00976/miR137/OTUD7B established the ceRNA network modulating PC cell proliferation and tumor growth. Conclusion The present study demonstrates that linc00976 enhances the proliferation and invasion ability of PC cells by upregulating OTUD7B expression, which was a target of miR-137. Ultimately, OTUD7B mediates EGFR and MAPK signaling pathway, suggesting that linc00976/miR-137/OTUD7B/EGFR axis may act as a potential biomarker and therapeutic target for PC.

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