Synergistic Inhibitory Effects of 5-Aza-2'-Deoxycytidine and Cisplatin on Urothelial Carcinoma Growth via Suppressing TGFBI-MAPK Signaling Pathways

2021 ◽  
Author(s):  
Donghao Shang ◽  
Gang Li ◽  
Caixing Zhang ◽  
Yuting Liu
Keyword(s):  
Growth Factor ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Combined Treatment ◽  
Mapk Signaling ◽  
Regulatory Genes ◽  
Mapk Signaling Pathway ◽  
Receptor Interaction ◽  
Synergistic Mechanism ◽  
Mapk Signaling Pathways

This study is to reveal the gene transcriptional alteration, possible molecular mechanism, and pathways involved in the synergy of 5-aza-2'-deoxycytidine (DAC) and CDDP in UC. Two UC cell lines, 5637 and T24, were used in the study. A cDNA microarray was carried out to identify critical genes in the synergistic mechanism of both agents against UC cells. The results showed that several key regulatory genes, such as interleukin 24(IL24), fibroblast growth factor 1(FGF1), and transforming growth factor beta-induced (TGFBI), were identified and may play critical roles in the synergy of DAC and CDDP in UC. Pathway enrichment suggested that many carcinogenesis-related pathways, such as ECM-receptor interaction and MAPK signaling pathways, may participate in the synergy of both agents. Our results suggested that TGF-β1 stimulates the phosphorylation levels of ERK1/2 and p38 via increasing TGFBI expression, TGFBI-MAPK signaling pathway plays an important role in the synergy of DAC and CDDP against UC. Therefore, we revealed the synergistic mechanism of DAC and CDDP in UC, several key regulatory genes play critical roles in the synergy of combined treatment, and TGFBI-MAPK signaling pathway may be an important potential target of these two agents.

scholarly journals TRF-Val-CAC-016 Modulates the Transduction of CACNA1d-Mediated MAPK Signaling Pathways to Suppress the Proliferation of Gastric Carcinoma

2022 ◽  
Author(s):  
Weiguo Xu ◽  
Junyu Zheng ◽  
Xiao Wang ◽  
Bin Zhou ◽  
Huanqiu Chen ◽  
...  
Keyword(s):  
Gastric Carcinoma ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Luciferase Reporter ◽  
Trna Derivatives ◽  
Mapk Signaling Pathways

Abstract Background: As a new kind of non-coding RNAs (ncRNAs), tRNA derivatives play an important role in gastric carcinoma (GC). Nevertheless, the underlying mechanism tRNA derivatives were involved in was rarely illustrated. Methods: We screened out the tRNA derivative, tRF-Val-CAC-016, based on the tsRNA sequencing and demonstrated the effect tRF-Val-CAC-016 exerted on GC proliferation in vitro and in vivo. We applied Dual-luciferase reporter assay, RIP assay, and bioinformatic analysis to discover the downstream target of tRF-Val-CAC-016. Then CACNA1d was selected, and the oncogenic characteristics were verified. Subsequently, we detected the possible regulation of the canonical MAPK signaling pathway to further explore the downstream mechanism of tRF-Val-CAC-016. Results: As a result, we found that tRF-Val-CAC-016 was low-expressed in GC, and upregulation of tRF-Val-CAC-016 could significantly suppress the proliferation of GC cell lines. Meanwhile, tRF-Val-CAC-016 regulated the canonical MAPK signaling pathway by targeting CACNA1d. Conclusions: tRF-Val-CAC-016 modulates the transduction of CACNA1d-mediated MAPK signaling pathways to suppress the proliferation of gastric carcinoma. This study discussed the function and mechanism of tRF-Val-CAC-016 in GC for the first time. The pioneering work has contributed to our present understanding of tRNA derivative, which might provide an alternative mean for the targeted therapy of GC.

scholarly journals Targeting ERK-Hippo Interplay in Cancer Therapy

2020 ◽  
Vol 21 (9) ◽  
pp. 3236 ◽  
Author(s):  
Karel Vališ ◽  
Petr Novák
Keyword(s):  
Cancer Therapy ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Cross Talk ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Mitogen Activated Protein Kinase ◽  
Cancer Therapies ◽  
Anti Cancer ◽  
Targeted Inhibition

Extracellular signal-regulated kinase (ERK) is a part of the mitogen-activated protein kinase (MAPK) signaling pathway which allows the transduction of various cellular signals to final effectors and regulation of elementary cellular processes. Deregulation of the MAPK signaling occurs under many pathological conditions including neurodegenerative disorders, metabolic syndromes and cancers. Targeted inhibition of individual kinases of the MAPK signaling pathway using synthetic compounds represents a promising way to effective anti-cancer therapy. Cross-talk of the MAPK signaling pathway with other proteins and signaling pathways have a crucial impact on clinical outcomes of targeted therapies and plays important role during development of drug resistance in cancers. We discuss cross-talk of the MAPK/ERK signaling pathway with other signaling pathways, in particular interplay with the Hippo/MST pathway. We demonstrate the mechanism of cell death induction shared between MAPK/ERK and Hippo/MST signaling pathways and discuss the potential of combination targeting of these pathways in the development of more effective anti-cancer therapies.

scholarly journals Identification of the Crucial Gene in Overflow Arteriovenous Fistula by Bioinformatics Analysis

2021 ◽  
Vol 12 ◽  
Author(s):  
Zhengde Zhao ◽  
Qining Fu ◽  
Liangzhu Hu ◽  
Yangdong Liu
Keyword(s):  
Signaling Pathways ◽  
Signaling Pathway ◽  
Intimal Hyperplasia ◽  
Enrichment Analysis ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Biological Processes ◽  
Hub Genes ◽  
Av Fistula ◽  
Core Genes

Objective: The aim was to study the preliminary screening of the crucial genes in intimal hyperplasia in the venous segment of arteriovenous (AV) fistula and the underlying potential molecular mechanisms of intimal hyperplasia with bioinformatics analysis.Methods: The gene expression profile data (GSE39488) was analyzed to identify differentially expressed genes (DEGs). We performed Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis of DEGs. Gene set enrichment analysis (GSEA) was used to understand the potential activated signaling pathway. The protein–protein interaction (PPI) network was constructed with the STRING database and Cytoscape software. The Venn diagram between 10 hub genes and gene sets of 4 crucial signaling pathways was used to obtain core genes and relevant potential pathways. Furthermore, GSEAs were performed to understand their biological functions.Results: A total of 185 DEGs were screened in this study. The main biological function of the 111 upregulated genes in AV fistula primarily concentrated on cell proliferation and vascular remodeling, and the 74 downregulated genes in AV fistula were enriched in the biological function mainly relevant to inflammation. GSEA found four signaling pathways crucial for intimal hyperplasia, namely, MAPK, NOD-like, Cell Cycle, and TGF-beta signaling pathway. A total of 10 hub genes were identified, namely, EGR1, EGR2, EGR3, NR4A1, NR4A2, DUSP1, CXCR4, ATF3, CCL4, and CYR61. Particularly, DUSP1 and NR4A1 were identified as core genes that potentially participate in the MAPK signaling pathway. In AV fistula, the biological processes and pathways were primarily involved with MAPK signaling pathway and MAPK-mediated pathway with the high expression of DUSP1 and were highly relevant to cell proliferation and inflammation with the low expression of DUSP1. Besides, the biological processes and pathways in AV fistula with the high expression of NR4A1 similarly included the MAPK signaling pathway and the pathway mediated by MAPK signaling, and it was mainly involved with inflammation in AV fistula with the low expression of NR4A1.Conclusion: We screened four potential signaling pathways relevant to intimal hyperplasia and identified 10 hub genes, including two core genes (i.e., DUSP1 and NR4A1). Two core genes potentially participate in the MAPK signaling pathway and might serve as the therapeutic targets of intimal hyperplasia to prevent stenosis after AV fistula creation.

scholarly journals C11 cyclopentenone from the ascidian Diplosoma sp. prevents epidermal growth factor-induced transformation of JB6 cells

2012 ◽  
Vol 2 (1) ◽  
pp. 4 ◽  
Author(s):  
Sergey N. Fedorov ◽  
Sergey A. Dyshlovoy ◽  
Larisa K. Shubina ◽  
Alla Guzii ◽  
Alexandra S. Kuzmich ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Signaling Pathways ◽  
Cellular Response ◽  
Cell Transformation ◽  
Soft Agar ◽  
Mapk Signaling ◽  
Human Leukemia ◽  
Epidermal Growth ◽  
Mapk Signaling Pathways

C<sub>11</sub> cyclopentenone, 5-hydroxy-7-prop-2-en- (E)-ylidene-7,7a-dihydro-2H-cyclopenta[b] pyran-6-one, isolated earlier from the sponges and ascidians, is known as a natural product possessing antimicrobial and cytotoxic properties. However, its cancer preventive activity has not been studied. Cancer preventive and proapoptotic properties of the compound as well as its effect on the main Mitogen- Activated Protein-Kinase (MAPK) signaling pathways were examined by the methods of epidermal growth factor- induced (EGFinduced) JB6 Cl41 P+ cell transformation in soft agar, flow cytometry, and MTS test of cell viability. Results: the compound inhibits EGFinduced neoplastic JB6 Cl41 P+ cell transformation in soft agar and induces apoptosis of HL-60 and THP-1 human leukemia cells. Jun N-terminal Kinase and p38 MAPK signaling pathways are involved in the cellular response to the treatment by the compound. Conclusions: 5-hydroxy-7-prop-2-en-(E)-ylidene- 7,7a-dihydro-2H-cyclopenta[b]pyran-6- one and other related marine C11 cyclopentenones have potential for development of a new antitumor agent in cancer prophylactics and should be further investigated.

Sign in / Sign up

Export Citation Format

Share Document