DataVXAdvanced SciencePaper
journal article·2025-08Open access

HPD is an RNA‐Binding Protein Sustaining Ovarian Cancer Cell Glycolysis, Tumor Growth, and Drug Resistance

Fei Xie, Han Zhang, Xintong Dai, Mengxin Tu, Chenxi Yu, Lumeng Liu, Yajuan Guo, Huanran Sun, Qingle Gao, Jiyan Wang, Mingming Sun, Qijun Zhang, Taoyuan Wang, Tao He, Zhen Li, Yanping Li, Tao Wang, Jianguo Zhao, Zhongjie Chen, Chunze Zhang, Shuai Zhang, Changliang Shan

Advanced Science· Volume 12· Issue 30
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Source abstract

Abstract

Abstract 4‐hydroxyphenylpyruvate dioxygenase (HPD) is an important metabolic enzyme in the tyrosine metabolic pathway and displays aberrant expression and function in cancer. Unexpectedly, it is discovered that HPD functions as an RNA‐binding protein (RBP) to drive ovarian cancer progression. HPD is shown to bind to the RRACH motif of these target mRNAs through its two dsRNA binding domains (RBDs), resulting in increased global mRNA translation. In particular, HPD binding is demonstrated to mediate translation of glycolytic enzymes triosephosphate isomerase (TPI) and alpha‐enolase (ENO1) mRNAs, which facilitates ovarian cancer glycolysis and tumor growth. Thus, targeting the RBD domain of HPD disrupts its RNA binding ability, leading to blocking glycolysis flux, tumor growth, and enhancing drug response. HPD is a novel RNA‐binding protein, and this moonlighting function highlights the knowledge of HPD in regulating cancer development and drug response beyond only as a metabolic enzyme.
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Research context

OpenAlex topics: RNA modifications and cancer · RNA Research and Splicing · RNA and protein synthesis mechanisms

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

Affiliations

State Key Laboratory of Medicinal Chemical Biology College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research Nankai University Tianjin 300350 China

Department of Pharmacology School of Pharmacy Fourth Military Medical University Xi'an 710032 China

Cardiothoracic Surgery Department Characteristic Medical Center of the Chinese People's Armed Police Force Tianjin 300162 China

Department of Pathology Characteristic Medical Center of The Chinese People's Armed Police Force Tianjin 300162 China

Guangzhou Key Laboratory for Clinical Rapid Diagnosis and Early Warning of Infectious Diseases KingMed School of Laboratory Medicine Guangzhou Medical University Guangzhou Guangdong 510180 China

Department of Pathology and Institute of Precision Medicine Jining Medical University Jining 272067 China

Tianjin Key Laboratory of Human Development and Reproductive Regulation Tianjin Central Hospital of Obstetrics and Gynecology Tianjin 300110 China

Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital National Clinical Research Center for Cancer Key Laboratory of Cancer Prevention and Therapy Tianjin's Clinical Research Center for Cancer Tianjin 300060 China

Department of Radiation Oncology Tianjin Cancer Hospital Airport Hospital Tianjin 300308 China

Department of Colorectal Surgery Tianjin Union Medical Center and The First Affiliated Hospital of Nankai University Tianjin 300121 China

School of Integrative Medicine Tianjin University of Traditional Chinese Medicine Tianjin 301617 China

Funding

National Natural Science Foundation of China · Natural Science Foundation of Tianjin Municipality · China Postdoctoral Science Foundation · Basic and Applied Basic Research Foundation of Guangdong Province

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