Purpurogallin is a novel mitogen‐activated protein kinase kinase 1/2 inhibitor that suppresses esophageal squamous cell carcinoma growth in vitro and in vivo

Abstract Background Esophageal squamous cell carcinoma (ESCC) is an aggressive and lethal cancer with a low 5 year survival rate. Identification of new therapeutic targets and its inhibitors remain essential for ESCC prevention and treatment. Methods TYK2 protein levels were checked by immunohistochemistry. The function of TYK2 in cell proliferation was investigated by MTT [(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] and anchorage-independent cell growth. Computer docking, pull-down assay, surface plasmon resonance, and kinase assay were used to confirm the binding and inhibition of TYK2 by cirsiliol. Cell proliferation, western blot and patient-derived xenograft tumor model were used to determine the inhibitory effects and mechanism of cirsiliol in ESCC. Results TYK2 was overexpressed and served as an oncogene in ESCC. Cirsiliol could bind with TYK2 and inhibit its activity, thereby decreasing dimer formation and nucleus localization of signal transducer and activator of transcription 3 (STAT3). Cirsiliol could inhibit ESCC growth in vitro and in vivo. Conclusions TYK2 is a potential target in ESCC, and cirsiliol could inhibit ESCC by suppression of TYK2.

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CXCL6 fuels the growth and metastases of esophageal squamous cell carcinoma cells both in vitro and in vivo through upregulation of PD‐L1 via activation of STAT3 pathway

Journal of Cellular Physiology ◽

10.1002/jcp.30236 ◽

2020 ◽

Author(s):

Shutao Zheng ◽

Tongxue Shen ◽

Qing Liu ◽

Tao Liu ◽

Aerziguli Tuerxun ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Esophageal Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Carcinoma Cells ◽

Stat3 Pathway

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Activation of AtMEK1, an Arabidopsis mitogen‐activated protein kinase kinase, in vitro and in vivo : analysis of active mutants expressed in E. coli and generation of the active form in stress response in seedlings

The Plant Journal ◽

10.1046/j.0960-7412.2001.01246.x ◽

2002 ◽

Vol 29 (5) ◽

pp. 637-647 ◽

Cited By ~ 88

Author(s):

Daisuke Matsuoka ◽

Takashi Nanmori ◽

Ken‐ichi Sato ◽

Yasuo Fukami ◽

Ushio Kikkawa ◽

...

Keyword(s):

Stress Response ◽

Protein Kinase ◽

Active Form ◽

Mitogen Activated Protein Kinase ◽

E Coli ◽

Mitogen Activated Protein ◽

In Vivo Analysis ◽

Protein Kinase Kinase

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Long Non-Coding RNA CCAT2 Promotes the Development of Esophageal Squamous Cell Carcinoma by Inhibiting miR-200b to Upregulate the IGF2BP2/TK1 Axis

Frontiers in Oncology ◽

10.3389/fonc.2021.680642 ◽

2021 ◽

Vol 11 ◽

Author(s):

Xiaodan Wu ◽

Yihui Fan ◽

Yupeng Liu ◽

Biao Shen ◽

Haimin Lu ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Esophageal Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Clinical Samples ◽

Non Coding Rna

Long non-coding RNAs (lncRNAs) have been shown to play important roles in human cancers, including esophageal squamous cell carcinoma (ESCC). In the current study, we identified CCAT2 as a relevant lncRNA and investigated its role in the progression of ESCC. RT-qPCR was adopted to detect CCAT2 expression in collected clinical samples, ESCC cell lines, and a normal cell line. We tested the correlation between CCAT2 expression and the prognosis of ESCC. RT-qPCR or immunoblotting was adopted to detect the expression of relevant factors in ESCC tissues or cells. Cell proliferation, apoptosis, migration, and invasion were examined by colony formation assay, flow cytometry, scratch assay, and Transwell assay, respectively, while subcutaneous tumorigenesis in nude mice was adopted to examine the role of CCAT2 in tumorigenesis of ESCC cells in vivo. Bioinformatics analysis, dual luciferase reporter assay, and RIP were conducted for the target relationship profiling. Me-RIP was adopted to detect m6A modification level of TK1 in ESCC tissues or cells. Upregulated CCAT2, IGF2BP2, and TK1 expression and inhibited miR-200b expression were observed in ESCC cells and tissues. CCAT2 bound to miR-200b and reduced its expression, leading to upregulated IGF2BP2 expression. IGF2BP2 improved TK1 mRNA stability to enhance its expression by recognizing its m6A modification. CCAT2 promoted the migration and invasion of ESCC cells in vitro, and tumorigenesis in vivo by upregulating TK1 expression, while overexpression of miR-200b reversed these effects of CCAT2. Overall, this study suggests that CCAT2 competitively binds to miR-200b to alleviate its inhibitory effects on IGF2BP2 expression, resulting in elevated TK1 expression, and an ensuing promotion of the development of ESCC.

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A novel oral camptothecin analog, gimatecan, exhibits superior antitumor efficacy than irinotecan toward esophageal squamous cell carcinoma in vitro and in vivo

Cell Death and Disease ◽

10.1038/s41419-018-0700-0 ◽

2018 ◽

Vol 9 (6) ◽

Cited By ~ 8

Author(s):

Jianling Zou ◽

Shuang Li ◽

Zuhua Chen ◽

Zhihao Lu ◽

Jing Gao ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Esophageal Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Antitumor Efficacy

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Circ_DLG1 facilitates esophageal squamous cell carcinoma progression by mediating miR-338-3p/MAP3K9 axis via activating MAPK/ERK pathway

10.21203/rs.3.rs-16608/v1 ◽

2020 ◽

Author(s):

Yixuan Yang ◽

Bing Zhu ◽

Zhaofeng Ning ◽

Xiaodong Wang ◽

Zhaoxia Li ◽

...

Keyword(s):

Cell Cycle ◽

Squamous Cell Carcinoma ◽

Esophageal Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Mitogen Activated Protein Kinase ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Erk Pathway

Abstract Background: Esophageal squamous cell carcinoma (ESCC) is an aggressive malignancy with a high incidence and poor prognosis. The document of circular RNAs (circRNAs) is frequently associated with cancer development. This study intended to explore the functional mechanism of circ_DLG1 in ESCC.Methods: The expression of circ_DLG1, miR-338-3p and Mitogen-Activated Protein Kinase Kinase Kinase 9 (MAP3K9) was measured by quantitative real-time polymerase chain reaction (qRT-PCR). Cell cycle, proliferation, migration and invasion were performed for functional analysis using flow cytometry, 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) and transwell assay, respectively. The protein levels of MAP3K9, p38, phosphor p38 (p-p38), ERK1/2, phosphor ERK1/2 (p-ERK1/2) were detected by western blot. Bioinformatics tool for target prediction used the online tool starBase. Dual-luciferase reporter assay was performed to verify the target relationship. The animal experiments were performed to ascertain the role of circ_DLG1 in vivo.Results: The expression of circ_DLG1 was elevated in ESCC tissues, plasma and cells. Circ_DLG1 knockdown inhibited cell cycle, proliferation, migration and invasion. MAP3K9 was highly expressed in ESCC tissues and cells, and its overexpression rescued the effects of circ_DLG1 knockdown. MiR-338-3p was a link between circ_DLG1 and MAP3K9, and circ_DLG1 regulated the expression of MAP3K9 by targeting miR-338-3p. The MAPK/ERK pathway was involved in the circ_DLG1/miR-338-3p/MAP3K9 regulatory axis. Circ_DLG1 knockdown blocked the tumor growth in vivo by regulating miR-338-3p and MAP3K9.Conclusion: Circ_DLG1 contributed to the malignant progression of ESCC by mediating the miR-338-3p/MAP3K9 axis via activating the MAPK/ERK signaling pathway. This paper provided a novel action mode of circ_DLG1 in ESCC.

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Exosomal lncRNA ZFAS1 regulates esophageal squamous cell carcinoma cell proliferation, invasion, migration and apoptosis via microRNA-124/STAT3 axis

Journal of Experimental & Clinical Cancer Research ◽

10.1186/s13046-019-1473-8 ◽

2019 ◽

Vol 38 (1) ◽

Cited By ~ 18

Author(s):

Zhirong Li ◽

Xuebo Qin ◽

Wei Bian ◽

Yishuai Li ◽

Baoen Shan ◽

...

Keyword(s):

Cell Proliferation ◽

Squamous Cell Carcinoma ◽

Esophageal Squamous Cell Carcinoma ◽

Tumor Growth ◽

Cell Carcinoma ◽

Squamous Cell ◽

Migration And Invasion ◽

Donor Cells

Abstract Background In recent years, long non-coding RNAs (lncRNAs) are of great importance in development of different types of tumors, while the function of lncRNA ZFAS1 is rarely discussed in esophageal squamous cell carcinoma (ESCC). Therefore, we performed this study to explore the expression of exosomal lncRNA ZFAS1 and its molecular mechanism on ESCC progression. Methods Expression of ZFAS1 and miR-124 in ESCC tissues was detected. LncRNA ZFAS1 was silenced to detect its function in the biological functions of ESCC cells. A stable donor and recipient culture model was established. Eca109 cells transfected with overexpressed and low expressed ZFAS1 plasmid and miR-124 inhibitor labeled by Cy3 were the donor cells, and then co-cultured with recipient cells to observe the transmission of Cy3-ZFAS1 between donor cells and recipient cells. The changes of cell proliferation, apoptosis, invasion, and migration in recipient cells were detected. The in vivo experiment was conducted for verifying the in vitro results. Results LncRNA ZFAS1 was upregulated and miR-124 was down-regulated in ESCC tissues. Silencing of ZFAS1 contributed to suppressed proliferation, migration, invasion and tumor growth in vitro and induced apoptosis of ESCC cells. LncRNA ZFAS1 was considered to be a competing endogenous RNA to regulate miR-124, thereby elevating STAT3 expression. Exosomes shuttled ZFAS1 stimulated proliferation, migration and invasion of ESCC cells and restricted their apoptosis with increased STAT3 and declined miR-124. Furthermore, in vivo experiment suggested that elevated ZFAS1-exo promoted tumor growth in nude mice. Conclusion This study highlights that exosomal ZFAS1 promotes the proliferation, migration and invasion of ESCC cells and inhibits their apoptosis by upregulating STAT3 and downregulating miR-124, thereby resulting in the development of tumorigenesis of ESCC.

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