MAPK Signaling Pathway: A Central Target in Pancreatic Cancer Therapeutics

2020 ◽  
pp. 99-113
Author(s):  
Sahdeo Prasad ◽  
Sanjay K. Srivastava
Keyword(s):  
Pancreatic Cancer ◽  
Signaling Pathway ◽  
Cancer Therapeutics ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Central Target

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.

scholarly journals JWA gene regulates PANC-1 pancreatic cancer cell behaviors through MEK-ERK1/2 of the MAPK signaling pathway

2014 ◽  
Vol 8 (4) ◽  
pp. 1859-1863 ◽  
Author(s):  
YUAN-YUAN WU ◽  
TIE-LIANG MA ◽  
ZHI-JUN GE ◽  
JIE LIN ◽  
WEI-LIANG DING ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Signaling Pathway ◽  
Cancer Cell ◽  
Pancreatic Cancer Cell ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Cell Behaviors

scholarly journals Metformin inhibited pancreatic cancer growth by upregulating miR-143/145 cluster and suppressing MAPK signaling pathway

HPB ◽  
2019 ◽  
Vol 21 ◽  
pp. S257-S258 ◽  
Author(s):  
Yaolin Xu ◽  
Zizhen Wu ◽  
Peng Yuan ◽  
Chunhui Jin ◽  
Yueming Zhang ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Signaling Pathway ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Cancer Growth

scholarly journals Circular RNA hsa_circ_0006117 Facilitates Pancreatic Cancer Progression by Regulating the miR-96-5p/KRAS/MAPK Signaling Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
Tao Liu ◽  
Lei Zhou ◽  
Zhiwei He ◽  
Yankun Chen ◽  
Xueyi Jiang ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Circular Rna ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Mitogen Activated Protein Kinase ◽  
Luciferase Reporter ◽  
Molecular Characteristics ◽  
Dependent Manner

Circular RNAs (circRNAs) play key roles in many malignant tumors, including pancreatic cancer (PC); however, whether circular RNA hsa_circ_0006117, a newly identified circRNA, has a role in PC has not been investigated. Here, in order to elucidate the role and potential molecular mechanisms of circRNAs, we utilized bioinformatic tolls to screen the differentially expressed circRNAs in PC. Subsequently, circular RNA hsa_circ_0006117 was identified as being highly expressed in PC tissues in a screen of two GEO datasets, which was further verified in PC cell lines and tissues. Then, its molecular characteristics were investigated using methods such as Sanger sequencing and fluorescence in situ hybridization (FISH). Functional experiments subsequently indicated that circular RNA hsa_circ_0006117 facilitated the malignant behaviors of PC cells, prompting that it plays an oncogenic role in PC. Moreover, we found that circular RNA hsa_circ_0006117 exerts its PC-promoting effects via activating the KRAS/mitogen-activated protein kinase (MAPK) signaling pathway. Through bioinformatics exploration and dual-luciferase reporter assays, miR-96-5p was identified as a downstream target of circular RNA hsa_circ_0006117. A series of assays confirmed that circular RNA hsa_circ_0006117 acted as a miR-96-5p sponge, thereby promoting the malignant features of PC in a miR-96-5p/KRAS axis-dependent manner. Taken together, our study indicated, for the first time, that the specifically highly expressed circular RNA hsa_circ_0006117 facilitates PC progression via the modulation of the miR-96-5p/KRAS/MAPK signaling pathway and might be a hopeful therapeutic target for PC.

scholarly journals Calreticulin promotes EGF-induced EMT in pancreatic cancer cells via Integrin/EGFR-ERK/MAPK signaling pathway

2017 ◽  
Vol 8 (10) ◽  
pp. e3147-e3147 ◽  
Author(s):  
Weiwei Sheng ◽  
Chuanping Chen ◽  
Ming Dong ◽  
Guosen Wang ◽  
Jianping Zhou ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Erk Mapk ◽  
Pancreatic Cancer Cells

MAPK: A Key Player in the Development and Progression of Stroke

2020 ◽  
Vol 19 (4) ◽  
pp. 248-256
Author(s):  
Yangmin Zheng ◽  
Ziping Han ◽  
Haiping Zhao ◽  
Yumin Luo
Keyword(s):  
Ischemic Stroke ◽  
Signaling Pathway ◽  
Complex Disease ◽  
Therapeutic Targets ◽  
Cell Types ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Effective Prevention ◽  
Prevention And Treatment ◽  
Different Cell Types

Conclusion: Stroke is a complex disease caused by genetic and environmental factors, and its etiological mechanism has not been fully clarified yet, which brings great challenges to its effective prevention and treatment. MAPK signaling pathway regulates gene expression of eukaryotic cells and basic cellular processes such as cell proliferation, differentiation, migration, metabolism and apoptosis, which are considered as therapeutic targets for many diseases. Up to now, mounting evidence has shown that MAPK signaling pathway is involved in the pathogenesis and development of ischemic stroke. However, the upstream kinase and downstream kinase of MAPK signaling pathway are complex and the influencing factors are numerous, the exact role of MAPK signaling pathway in the pathogenesis of ischemic stroke has not been fully elucidated. MAPK signaling molecules in different cell types in the brain respond variously after stroke injury, therefore, the present review article is committed to summarizing the pathological process of different cell types participating in stroke, discussed the mechanism of MAPK participating in stroke. We further elucidated that MAPK signaling pathway molecules can be used as therapeutic targets for stroke, thus promoting the prevention and treatment of stroke.

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