Article
Biochemistry & Molecular Biology
Qiuxia Yan, Peng Zeng, Xiuqin Zhou, Xiaoying Zhao, Runqiang Chen, Jing Qiao, Ling Feng, Zhenjie Zhu, Guozhi Zhang, Cairong Chen
Summary: The study revealed that RBMX is significantly downregulated in bladder cancer tissues and inhibits tumorigenicity and progression through interfering with PKM alternative splicing. This suggests RBMX may serve as a novel prognostic biomarker for clinical intervention in bladder cancer.
Article
Chemistry, Medicinal
Xingchen Liu, Cheng Wang, Shang Li, Lailiang Qu, Fucheng Yin, Dehua Lu, Heng Luo, Xinye Chen, Zhongwen Luo, Ningjie Cui, Xiaobing Wang, Lingyi Kong
Summary: In this study, a potential drug candidate 29e for treating CRC was designed to inhibit tumor growth by targeting PKM2 kinase, demonstrating significant antiproliferative effects in cell experiments and animal models.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biology
Jun-ichi Takino, Takuma Sato, Isamu Hiraishi, Kentaro Nagamine, Takamitsu Hori
Summary: Pancreatic cancer has a poor prognosis compared to other cancer types, largely due to its resistance to hypovascular environments. Recent studies have shown that decreased expression of HNRNPM in PDA tissues may contribute to the adaptation of cancer cells to hypovascular conditions.
Review
Plant Sciences
Long Wang, Fan Xu, Feng Yu
Summary: Plants have developed adaptation mechanisms to respond to environmental signals, and receptors/sensors play a crucial role in recognizing these signals. RNA metabolism is also important in regulating gene expression and protein synthesis. Recent advances in RNA biotechnology have shed light on the roles of RNA metabolism, particularly alternative splicing and translation, in response to environmental signals. Understanding these mechanisms at the posttranscriptional level improves our ability to breed stress-tolerant plants for changing environments.
PLANT CELL AND ENVIRONMENT
(2023)
Article
Multidisciplinary Sciences
Shi-Hai Yan, Li-Mu Hu, Xue-Hui Hao, Jiang Liu, Xi-Ying Tan, Zhi-Rong Geng, Jing Ma, Zhi-Lin Wang
Summary: This study revealed the direct binding target protein of berberine in colorectal cancer cells, which is pyruvate kinase isozyme type M2 (PKM2). Berberine inhibits the progression of colorectal cancer through hydrophobic interaction and pi-pi interaction, and it also inhibits the reprogramming of glucose metabolism.
Article
Biochemistry & Molecular Biology
Gang Zhao, Hang Yuan, Qin Li, Jie Zhang, Yafei Guo, Tianyu Feng, Rui Gu, Deqiong Ou, Siqi Li, Kai Li, Ping Lin
Summary: This study uncovers the significant role of DDX39B in modulating glycolytic reprogramming and aggressive progression in colorectal cancer (CRC). The upregulation of DDX39B is associated with liver metastases and aggressive phenotypes in CRC patients. Mechanistically, DDX39B activates PKM2 by suppressing its ubiquitination and degradation, leading to enhanced glucose uptake and lactate production. DDX39B also accelerates the nuclear translocation of PKM2 to transactivate oncogenes and glycolysis-related genes, promoting CRC growth and metastasis. Furthermore, blocking PKM2 nuclear translocation or glycolytic inhibition efficiently abolishes DDX39B-triggered malignant development in CRC, highlighting DDX39B as a potential therapeutic target.
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2022)
Article
Biochemistry & Molecular Biology
Yudi Ma, Xiaohui Lai, Zhongling Wen, Ziling Zhou, Minkai Yang, Qingqing Chen, Xuan Wang, Feng Mei, Liu Yang, Tongming Yin, Shucun Sun, Guihua Lu, Jinliang Qi, Hongyan Lin, Hongwei Han, Yonghua Yang
Summary: The Warburg effect is essential for tumor proliferation, but reversing it can lead to a novel anti-cancer strategy. Two key enzymes in tumor glucose metabolism pathway, PKM2 and PDK1, not only contribute to the Warburg effect, but also serve as druggable targets for CRC. A series of benzenesulfonyl shikonin derivatives were designed to simultaneously regulate PKM2 and PDK1. Among them, compound Z10 acted as a PKM2 activator and PDK1 inhibitor, significantly inhibiting glycolysis and remodeling tumor metabolism. In addition, Z10 inhibited CRC cell proliferation and migration, and induced apoptosis. Furthermore, Z10 showed in vivo anti-tumor activity with lower toxicity compared to shikonin. Our findings suggest that altering tumor energy metabolism through multi-target synergies is feasible, and Z10 could be a potential anti-CRC agent.
BIOORGANIC CHEMISTRY
(2023)
Article
Clinical Neurology
Wujun Zhao, Miaomiao Li, Shuai Wang, Zhuang Li, Han Li, Shaoyi Li
Summary: This study reveals the regulatory role of circSRRM4 in epilepsy and its correlation with the expression of PKM2 and the regulation of SRSF3. Silencing circSRRM4 can reduce the incidence and frequency of epilepsy and improve related pathological changes.
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
(2023)
Article
Medicine, General & Internal
Lianhua Liu, Wenyi Pang, Jixiang Liu, Shiqing Xu, Zhu Zhang, Risheng Hao, Jun Wan, Wanmu Xie, Xincao Tao, Peiran Yang, Lan Zhao, Zhenguo Zhai, Chen Wang
Summary: This study investigated the mechanisms of abnormal glucose metabolism in chronic thromboembolic pulmonary hypertension (CTEPH) and found that PKM2 and ROS play important roles in CTEPH. By suppressing the levels of PKM2 and ROS, the abnormal glucose metabolism, cell proliferation, and migration can be alleviated. The regulation of the hnRNPA1/PKM2 axis may be a potential therapeutic target for the treatment of CTEPH.
JOURNAL OF TRANSLATIONAL INTERNAL MEDICINE
(2023)
Article
Cell Biology
C. Ariano, F. Costanza, M. Akman, C. Riganti, D. Cora, E. Casanova, E. Astanina, V. Comunanza, F. Bussolino, G. Doronzo
Summary: Melanomas are characterized by dysregulation of MAPK pathway, glycolysis, and TCA cycle, and the oncogenic transcription factor EB (TFEB) controls melanoma tumor growth through regulating ERK1/2 activity and metabolism. TFEB negatively regulates DUSP-1, dephosphorylates ERK1/2, and inhibits melanoma cell proliferation. TFEB also influences glucose, glutamine, and cholesterol metabolism, affecting glycolysis, glutaminolysis, and oxidative phosphorylation. TFEB silencing impairs cholesterol synthesis, glucose and glutamine uptake, and reverses TCA cycle, leading to fatty acid production. In a melanoma model, TFEB silencing reduces tumor growth, increases DUSP-1 level, and inhibits ERK1/2 action, indicating the importance of TFEB in melanoma cell behavior and metabolic pathways.
CELL DEATH & DISEASE
(2023)
Review
Medicine, General & Internal
Shengfeng Deng, Peng Yi, Mingliang Xu, Qian Yi, Jianguo Feng
Summary: Glucose metabolism is vital for brain activity, and its decrease in Alzheimer's disease (AD) may play a fundamental role in its development. Recent studies show that alternative splicing events of certain genes regulate various processes in glucose metabolism, affecting glucose uptake, glycolysis, and signaling pathways. Aberrant alternative splicing, which alters protein diversity and activity, is pivotal in understanding AD development. This review summarizes the alternative splicing events of glucose metabolism-related genes in AD pathology and emphasizes the regulatory roles of splicing factors. Emerging therapeutic approaches targeting splicing factors for AD treatment are also discussed.
CHINESE MEDICAL JOURNAL
(2023)
Article
Medicine, Research & Experimental
Ganesh Satyanarayana, Ravi Chakra Turaga, Malvika Sharma, Siming Wang, Falguni Mishra, Guangda Peng, Xiaonan Deng, Jenny Yang, Zhi-Ren Liu
Summary: This study reveals that differentiation of myofibroblasts upregulates pyruvate kinase M2 (PKM2) and promotes PKM2 dimerization, which slows glycolysis and facilitates collagen synthesis and secretion. PKM2 activator inhibits progression of liver, lung, and pancreatic fibrosis in mouse models, while increasing NADPH production to protect myofibroblasts from apoptosis.
Article
Biochemistry & Molecular Biology
Rui Cheng, Lixing Xiao, Wenyang Zhou, Xiyun Jin, Zhaochun Xu, Chang Xu, Pingping Wang, Meng Luo, Mengyun Wang, Kexin Ma, Huimin Cao, Yan Huang, Xiaoyu Lin, Fenglan Pang, Yiqun Li, Qinghua Jiang
Summary: This study conducted a pan-cancer analysis of alternative splicing of splicing factors and identified 167 splicing factors with implications in regulating cancer-specific splicing patterns. The findings suggest that alternative splicing of splicing factors may serve as common regulators for alternative splicing in different cancers, highlighting its potential importance in tumorigenesis. Additionally, a splicing-derived neoepitopes database (ASPNs) was developed to provide putative alternative splicing-derived neoepitopes of 16 cancer types.
Article
Biochemistry & Molecular Biology
Jianyi Wang, Chuhan Wang, Le Li, Lirui Yang, Shuoshuo Wang, Xuelian Ning, Shuangshu Gao, Lili Ren, Anita Chaulagain, Jing Tang, Tianzhen Wang
Summary: Alternative splicing produces various mRNA isoforms through different splicing patterns of pre-mRNAs, influencing biodiversity and biological processes. It has been reported to be involved in the tumorigenesis of colorectal carcinoma. Understanding alternative splicing is crucial for studying the development of colorectal cancer.
MOLECULAR CARCINOGENESIS
(2021)
Review
Oncology
Zhi-Man Zhu, Fu-Chun Huo, Jian Zhang, Hong-Jian Shan, Dong-Sheng Pei
Summary: N6-methyladenosine (m6A) is the most prevalent internal mRNA modification in eukaryotes, and it significantly influences various aspects of RNA metabolism. Pre-mRNA alternative splicing, a process that generates multiple splice isoforms, contributes to protein diversity in mammals. There is crosstalk between m6A modification and alternative splicing, where m6A modifications on pre-mRNAs regulate alternative splicing patterns by recruiting specific RNA-binding proteins or directly influencing the interaction between proteins and RNAs. Alternative splicing can also impact the deposition or recognition of m6A modification on mRNAs.
CLINICAL AND TRANSLATIONAL MEDICINE
(2023)