Transcriptional upregulation of MAPK15 by NF-κB signaling boosts the efficacy of combination therapy with cisplatin and TNF-α

Wu, Dandan; Dai, Lijuan; Tan, Heng Wee; Zhao, Xiao‐Yun; Wei, Qi-Yao; Zhong, Qiu-Hua; Ji, Yan-Chen; Yin, Xiaohui; Yu, Feiyuan; Jin, Dong-Yan; Li, Shengqing; Lau, Andy T. Y.; Xu, Yan‐Ming

doi:10.1016/j.isci.2022.105459

Cited by 2 publications

(4 citation statements)

References 43 publications

(57 reference statements)

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“…However, MAPK15 IHC staining in normal tissue is relatively weak when compared with the malignant tissue (Supplementary Figure S1A,B). Combined with existing research showing that MAPK15 could boost DNA damage [14] and stimulate autophagy [10], we propose that when cells encounter hits, MAPK15 is upregulated, as a stress-activated protein, to enhance the DNA damage and cell death, which subsequently prevents abnormal cell accumulation and malignant transformation. On the other hand, those cells that lack MAPK15 upregulation are headed for a disastrous outcome-carcinogenesis.…”

Section: Discussionmentioning

confidence: 69%

“…Recently, our group has reported that MAPK15-mediated NF-κB activation enhances the arsenic trioxide-induced apoptosis through promoting the phosphorylation and degradation of IκBα, as well as the nuclear translocation of NF-κB in lung cancer cells [ 15 ]. Accordingly, we have demonstrated that the transcriptional upregulation of MAPK15 via NF-κB signaling boosts the efficacy of TNF-α-augmented cisplatin-induced cell apoptosis [ 14 ]. More recently, we clarify that MAPK15 interacts with NF-κB p50 and enters the nucleus, in which NF-κB p50 binds to the EP3 promoter and transcriptionally regulates the expression of EP3, thereby affecting the migration of lung adenocarcinoma [ 13 ].…”

Section: Discussionmentioning

confidence: 99%

“…The cells were maintained in a 5% CO 2 -humidified incubator at 37 • C. Transfections were performed with PEI reagent according to the manufacturer's instructions. The plasmids pcDNA4/HisMaxA-MAPK15 and pLKO.1-TRC-shMAPK15 have been described previously [14].…”

Section: Cell Culture and Transfectionmentioning

confidence: 99%

“…Our previous research revealed that MAPK15 promotes metastasis via its interaction with NF-κB subunit p50 and the transcriptional regulation of prostaglandin E2 receptor EP3 subtype in human non-small cell lung cancer (NSCLC) [ 13 ]. Moreover, our group has reported the pivotal role of MAPK15 and NF-κB signaling in boosting the efficacy of combination therapy with cisplatin and TNF-α, as well as increasing arsenic trioxide-induced cell apoptosis, in lung cancer cell lines [ 14 , 15 ]. However, the expression and regulation of MAPK15 are still unexplored in many other types of cancer.…”

Section: Introductionmentioning

confidence: 99%

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Mitogen-Activated Protein Kinase 15 Is a New Predictive Biomarker and Potential Therapeutic Target for Ovarian Cancer

Zhong,

Lau,

2023

IJMS

Self Cite

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Mitogen-activated protein kinase 15 (MAPK15) has been reported to be associated with several cancers. This study aimed to explore for the first time on the relationship between MAPK15 expression and cancer progression/drug responsiveness in ovarian carcinoma. To this end, MAPK15 expression level was examined by immunohistochemistry (IHC) staining of an ovarian tissue array (10 normal and 70 malignant samples). Drug sensitivity of ovarian cancer cell lines (including OVCAR3 and SKOV3) was measured by MTS assay. The modulation of MAPK15 expression in OVCAR3 and SKOV3 was verified by immunoblot and real-time PCR analyses. The prognostic value of MAPK15 in ovarian cancer patients was assessed using the Kaplan-Meier Plotter database and Gene Expression Omnibus (GEO) datasets. The IHC results showed that a high MAPK15 expression was negatively associated with the degree of differentiation, TNM stage, tumor size, and regional lymph node metastasis of ovarian carcinoma. Importantly, overexpressing MAPK15 increased cisplatin toxicity in ovarian carcinoma cells and online database analysis indicated that patients with high MAPK15 expression had favorable prognosis with/without chemotherapy. Taken together, our results indicate that a decreased MAPK15 expression is associated with advanced-stage ovarian cancer and unfavorable survival outcomes. MAPK15 may be a new biomarker for ovarian cancer, and the encouraging therapeutic strategy would be found by combining the regulation of MAPK15 expression.

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Section: Discussionmentioning

confidence: 69%

Section: Discussionmentioning

confidence: 99%

Section: Cell Culture and Transfectionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Mitogen-Activated Protein Kinase 15 Is a New Predictive Biomarker and Potential Therapeutic Target for Ovarian Cancer

Zhong,

Lau,

2023

IJMS

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The Atypical MAP Kinase MAPK15 Is Required for Lung Adenocarcinoma Metastasis via Its Interaction with NF-κB p50 Subunit and Transcriptional Regulation of Prostaglandin E2 Receptor EP3 Subtype

Zhao

et al. 2023

Cancers

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Studying the relatively underexplored atypical MAP Kinase MAPK15 on cancer progression/patient outcomes and its potential transcriptional regulation of downstream genes would be highly valuable for the diagnosis, prognosis, and potential oncotherapy of malignant tumors such as lung adenocarcinoma (LUAD). Here, the expression of MAPK15 in LUAD was detected by immunohistochemistry and its correlation with clinical parameters such as lymph node metastasis and clinical stage was analyzed. The correlation between the prostaglandin E2 receptor EP3 subtype (EP3) and MAPK15 expression in LUAD tissues was examined, and the transcriptional regulation of EP3 and cell migration by MAPK15 in LUAD cell lines were studied using the luciferase reporter assay, immunoblot analysis, qRT-PCR, and transwell assay. We found that MAPK15 is highly expressed in LUAD with lymph node metastasis. In addition, EP3 is positively correlated with the expression of MAPK15 in LUAD tissues, and we confirmed that MAPK15 transcriptionally regulates the expression of EP3. Upon the knockdown of MAPK15, the expression of EP3 was down-regulated and the cell migration ability was decreased in vitro; similarly, the mesenteric metastasis ability of the MAPK15 knockdown cells was inhibited in in vivo animal experiments. Mechanistically, we demonstrate for the first time that MAPK15 interacts with NF-κB p50 and enters the nucleus, and NF-κB p50 binds to the EP3 promoter and transcriptionally regulates the expression of EP3. Taken together, we show that a novel atypical MAPK and NF-κB subunit interaction promotes LUAD cell migration through transcriptional regulation of EP3, and higher MAPK15 level is associated with lymph node metastasis in patients with LUAD.

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Transcriptional upregulation of MAPK15 by NF-κB signaling boosts the efficacy of combination therapy with cisplatin and TNF-α

Cited by 2 publications

References 43 publications

Mitogen-Activated Protein Kinase 15 Is a New Predictive Biomarker and Potential Therapeutic Target for Ovarian Cancer

Mitogen-Activated Protein Kinase 15 Is a New Predictive Biomarker and Potential Therapeutic Target for Ovarian Cancer

The Atypical MAP Kinase MAPK15 Is Required for Lung Adenocarcinoma Metastasis via Its Interaction with NF-κB p50 Subunit and Transcriptional Regulation of Prostaglandin E2 Receptor EP3 Subtype

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