Histones Methyltransferase NSD3 Inhibits Lung Adenocarcinoma Glycolysis Through Interacting with PPP1CB to Decrease STAT3 Signaling Pathway

Yanling Zhou; Xintong Peng; Cheng Fang; Xin Peng; Jianing Tang; Zuli Wang; Yao Long; Jielin Chen; Yuanhao Peng; Zewen Zhang; Yanmin Zhou; Jun Tang; Jingzhong Liao; Desheng Xiao; Yongguang Tao; Ying Shi; Shuang Liu

doi:10.1002/advs.202400381

journal article·2024-10Open access

Histones Methyltransferase NSD3 Inhibits Lung Adenocarcinoma Glycolysis Through Interacting with PPP1CB to Decrease STAT3 Signaling Pathway

Yanling Zhou, Xintong Peng, Cheng Fang, Xin Peng, Jianing Tang, Zuli Wang, Yao Long, Jielin Chen, Yuanhao Peng, Zewen Zhang, Yanmin Zhou, Jun Tang, Jingzhong Liao, Desheng Xiao, Yongguang Tao, Ying Shi, Shuang Liu

Advanced Science· Volume 11· Issue 38

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Source abstract

Abstract

Abstract Histones methyltransferase NSD3 targeting H3K36 is frequently disordered and mutant in various cancers, while the function of NSD3 during cancer initiation and progression remains unclear. In this study, it is proved that downregulated level of NSD3 is linked to clinical features and poor survival in lung adenocarcinoma. In vivo, NSD3 inhibited the proliferation, immigration, and invasion ability of lung adenocarcinoma. Meanwhile, NSD3 suppressed glycolysis by inhibiting HK2 translation, transcription, glucose uptake, and lactate production in lung adenocarcinoma. Mechanistically, as an intermediary, NSD3 binds to PPP1CB and p‐STAT3 in protein levels, thus forming a trimer to dephosphorylate the level of p‐STAT3 by PPP1CB, leading to the suppression of HK2 transcription. Interestingly, the phosphorylation function of PPP1CB is related to the concentration of carbon dioxide and pH value in the culture environment. Together, this study revealed the critical non‐epigenetic role of NSD3 in the regulation of STAT3‐dependent glycolysis, providing a piece of compelling evidence for targeting the NSD3/PPP1CB/p‐STAT3 in lung adenocarcinoma.

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Research context

OpenAlex topics: Epigenetics and DNA Methylation · RNA modifications and cancer · Cancer-related molecular mechanisms research

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Oncology Institute of Medical Sciences National Clinical Research Center for Geriatric Disorders Institue of Medical Sciences Xiangya Hospital, Central South University Changsha Hunan 410008 China

Department of Hematology Xiangya Hospital, Central South University Changsha Hunan 410008 China

Key Laboratory of Carcinogenesis and Cancer Invasion Ministry of Education, Department of Pathology Xiangya Hospital, Central South University Changsha Hunan 410008 China

Cancer Research Institute School of Basic Medicine Central South University Changsha Hunan 410028 China

Department of Cardiac Surgery Xiangya Hospital, Central South University Changsha Hunan 410008 China

Department of Pathology Xiangya Hospital, Central South University Changsha Hunan 410008 China

Department of Liver Surgery Xiangya Hospital, Central South University Changsha Hunan 410008 China

Center for Tissue Engineering and Stem Cell Research Guizhou Medical University Guiyang Guizhou 561113 China

Department of Laboratory Medicine Xiangya Hospital, Central South University Changsha Hunan 410008 China

Funding

National Natural Science Foundation of China

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