Article
Oncology
Tao Han, Jing Tong, Mengxin Wang, Yu Gan, Bo Gao, Jiaxiang Chen, Youxun Liu, Qian Hao, Xiang Zhou
Summary: Olaparib is a widely used PARP inhibitor in the treatment of solid tumors. Its anti-tumor activity is achieved through the inhibition of PARP enzymes and blocking DNA repair. This study reveals that Olaparib activates the nucleolar stress-RPs-p53 pathway, leading to the activation of p53 and the inhibition of cancer cell survival and proliferation.
FRONTIERS IN ONCOLOGY
(2022)
Article
Cell Biology
Corinna Schreiner, Bianka Kernl, Petra Dietmann, Ricarda J. Riegger, Michael Kuehl, Susanne J. Kuehl
Summary: In this study, the researchers used Xenopus laevis as a model organism to investigate the role of Rpl5 in embryonic development. They showed that Rpl5 knockdown resulted in defects in cranial cartilage, eye formation, and brain development, similar to the clinical manifestations of Diamond Blackfan anemia (DBA). Further analyses revealed that Rpl5 functions through a common signaling pathway with c-Myc and Tp53, and that apoptosis is one of the main reasons for the observed phenotypes. This study provides new insights into the molecular background of ribosomopathies.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Pengbo Cao, Aiqing Yang, Peiyao Li, Xia Xia, Yuqing Han, Guangming Zhou, Rui Wang, Fei Yang, Yuanfeng Li, Ying Zhang, Ying Cui, Hongzan Ji, Lei Lu, Fuchu He, Gangqiao Zhou
Summary: The study revealed that the oncogene RRS1 on chromosome 8q promotes HCC development by regulating ribosome biogenesis activity and impacting the RPL11-MDM2-p53 pathway. Higher expression levels of RRS1 predict poor clinical outcomes in patients, especially in those with intact p53. This provides new potential targets for the treatment of this malignancy.
Article
Hematology
Marie-Francoise O'donohue, Lydie Da Costa, Marco Lezzerini, Sule Unal, Clement Joret, Marije Bartels, Eva Brilstra, Marijn Scheijde-Vermeulen, Ludivine Wacheul, Kim De Keersmaecker, Stijn Vereecke, Veerle Labarque, Manon Saby, Sophie D. Lefevre, Jessica Platon, Nathalie Montel-Lehry, Nathalie Laugero, Eric Lacazette, Koen van Gassen, Riekelt H. Houtkooper, Pelin Ozlem Simsek-Kiper, Thierry Leblanc, Nese Yarali, Arda Cetinkaya, Nurten A. Akarsu, Pierre-Emmanuel Gleizes, Denis L. J. Lafontaine, Alyson W. MacInnes
Summary: The study reports that individuals with biallelic HEATR3 variants exhibit bone marrow failure, short stature, dysmorphic features, and intellectual disability, similar to Diamond-Blackfan anemia. These variants destabilize a protein important for nuclear import, impacting ribosomal subunit formation and p53 tumor suppressor stabilization.
Article
Oncology
Hongyan Li, Hong Zhang, Guomin Huang, Zhitong Bing, Duling Xu, Jiadi Liu, Hongtao Luo, Xiaoli An
Summary: This study revealed that RPS27a interacts with RPL11, regulating p53 activation and playing crucial roles in LUAD progression. Knockdown of RPS27a enhances p53 activation, inhibits cell growth, and induces apoptosis.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2022)
Editorial Material
Cell Biology
Dan Lu, Ashwini Jambhekar, Galit Lahav
Summary: The study reveals that elevated levels of the transcription factor MYC enhance RNA production of target genes by prolonging the duration of transcriptional bursts rather than increasing their frequency.
Article
Hematology
Lei Yu, Philippe Lemay, Alexander Ludlow, Marie-Claude Guyot, Morgan Jones, Fatma F. Mohamed, Ghazi-Abdullah Saroya, Christopher Panaretos, Emily Schneider, Yu Wang, Greggory Myers, Rami Khoriaty, Qing Li, Renny Franceschi, James Douglas Engel, Vesa Kaartinen, Thomas L. Rothstein, Monica J. Justice, Zoha Kibar, Sharon A. Singh
Summary: Ribosome dysfunction is associated with various abnormal developmental and disease states in humans. The study identified a novel ENU mouse mutant with growth and skeletal defects, cardiac malformations, and increased mortality, caused by an intronic Rpl5 mutation leading to decreased ribosome generation and erythroid maturation delay. This mutant mouse model may be useful for studying the factors influencing variable penetrance observed in DBA.
Article
Cell Biology
Bojie Lin, Jiangying Zhu, Guoqian Yin, Mingde Liao, Guanyu Lin, Yuyong Yan, Dan Huang, Siding Lu
Summary: This study demonstrates that DLX5 promotes hair follicle stem cell (HFSC) differentiation by modulating the c-MYC/miR-29c-3p/NSD1 axis. DLX5 is highly expressed in differentiated HFSCs and transcriptionally activates c-MYC expression to induce HFSC differentiation. c-MYC suppresses miR-29c-3p expression, leading to NSD1-mediated HFSC differentiation.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Gastroenterology & Hepatology
Yuhong Luo, Yuqing Gao, Weiwei Liu, Yuan Yang, Jie Jiang, Ying Wang, Wei Tang, Shoumei Yang, Lulu Sun, Jie Cai, Xiaozhen Guo, Shogo Takahashi, Kristopher W. Krausz, Aijuan Qu, Lei Chen, Cen Xie, Frank J. Gonzalez
Summary: This study reveals that PRMT5 is an epigenetic executor of MYC, leading to repression of the transcriptional regulation of downstream genes that promote hepatocellular carcinogenesis. Through PRMT5 inhibition a mechanism-based therapeutic strategy for MYC-driven HCC is highlighted, which synergistically suppresses proliferation and enhances antitumor immunity, providing an opportunity to mitigate the resistance of immune-cold tumor to ICT.
Article
Chemistry, Medicinal
Qing Huang, Chunlan Pu, Lun Tan, Shirui Wang, Hongjia Zhang, Su Yu, Rui Deng, Dan Luo, Xinyu Ma, Rui Li
Summary: c-Myc protein, aberrantly expressed in colorectal cancer, can be effectively inhibited by a compound called B13. B13 not only suppresses the proliferation and migration of CRC cells, but also interferes with the expression of apoptosis pathway-related proteins. Additionally, B13 shows strong inhibition of tumor growth in animal models.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Tomoaki Ishida, Tomoe Ueyama, Dai Ihara, Yukihiro Harada, Sae Nakagawa, Kaho Saito, Shu Nakao, Teruhisa Kawamura
Summary: Induced pluripotent stem cells (iPSCs) have great potential in regenerative medicine and disease modeling, but their reprogramming efficiency is still low. In this study, researchers investigated the role of miR-17-92 in iPSC induction. They found that upregulation of miR-17-92 increased reprogramming efficiency, while deletion of the miR-17-92 cluster decreased efficiency. Further analysis revealed that miR-17-92 targets genes PTEN and p21, and their downregulation is disrupted by introducing the 3′ UTR of PTEN and p21, suggesting they act as competing endogenous RNAs (ceRNA). These findings provide insight into the underlying mechanism of iPSC reprogramming.
Article
Biochemistry & Molecular Biology
Derek A. Franklin, Shijie Liu, Aiwen Jin, Pengfei Cui, Zengli Guo, Kyle C. Arend, Nathaniel J. Moorman, Shenghui He, Gang Greg Wang, Yisong Y. Wan, Yanping Zhang
Summary: Recent discovery of the RP-MDM2-p53 signaling pathway implicates the role of p53 in ribosomopathies. Conditional RPL11 deletion in mice results in embryonic lethality or acute anemia depending on the stage of deletion. Mechanistically, RPL11 haploinsufficiency activates p53, impeding erythroid precursor differentiation and causing insufficient red blood cell development. Reducing p53 dosage or blocking the RP-MDM2-p53 pathway rescues the anemia phenotype in mice. These findings highlight the critical role of the RP-MDM2-p53 pathway in maintaining RP homeostasis and the molecular basis for RP deficiency-associated anemia.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Endocrinology & Metabolism
Piwei Huang, Minghui Wei, Shufan Ji, Maolin He
Summary: This study found that c-Myc regulates osteosarcoma cell proliferation by regulating the expression of RPL34.
JOURNAL OF BIOLOGICAL REGULATORS AND HOMEOSTATIC AGENTS
(2022)
Article
Biochemistry & Molecular Biology
Maria Anele Romeo, Maria Saveria Gilardini Montani, Andrea Arena, Rossella Benedetti, Gabriella D'Orazi, Mara Cirone
Summary: This study reveals another criminal alliance between oncogenes, such as c-Myc and mutp53, which play a key role in oncogenesis. The study found that inhibition of c-Myc downregulated mutp53 expression, impaired cell survival, and increased DNA damage in pancreatic cancer cells. Additionally, the study observed that c-Myc inhibition reduced the expression of MVK, a molecule belonging to the mevalonate pathway that controls mutp53 stability and contributes to cancer cell survival.
Article
Cell Biology
Hui Qin, Yan Tang, Yuan Mao, Xuehui Zhou, Tongrong Xu, Wenming Liu, Xin Su
Summary: This study investigates the role of C-MYC in pulmonary fibroblast proliferation in IPF. The results suggest that upregulated expression of C-MYC activates miR-9-5p to inhibit TBPL1, leading to increased proliferation and differentiation of pulmonary fibroblasts and the development of IPF.
CELLULAR SIGNALLING
(2022)
Article
Cell Biology
Qian Hao, Jiaxiang Chen, Junming Liao, Yingdan Huang, Yu Gan, Sarit Larisch, Shelya X. Zeng, Hua Lu, Xiang Zhou
Summary: ARTS and p53 collaborate closely in mitochondria-engaged apoptosis, with ARTS inducing apoptosis by antagonizing anti-apoptotic proteins and p53 activating the expression of ARTS.
CELL DEATH & DISEASE
(2021)
Article
Genetics & Heredity
Shanshan Wang, Xuan Zou, Yajie Chen, William C. Cho, Xiang Zhou
Summary: The study revealed that m^6A methylation regulators were significantly dysregulated in TNBC tissues, and could serve as a novel prognostic signature for predicting the survival of TNBC patients.
FRONTIERS IN GENETICS
(2021)
Article
Biochemistry & Molecular Biology
Fei Xu, Jiajia Li, Mengdong Ni, Jingyi Cheng, Haiyun Zhao, Shanshan Wang, Xiang Zhou, Xiaohua Wu
Summary: The study revealed that FBW7 suppresses tumor growth and progression in ovarian cancer by antagonizing YTHDF2-mediated BMF mRNA decay. This highlights the importance of the FBW7-YTHDF2 regulatory axis in ovarian cancer development and suggests potential therapeutic targets for the treatment of this disease.
Article
Oncology
Jieqiong Wang, Yajie Chen, Canhua Huang, Qian Hao, Shelya X. Zeng, Sara Omari, Yu Zhang, Xiang Zhou, Hua Lu
Summary: Valosin-containing protein (VCP) has been identified as a novel regulator of p53-R273H stability, stabilizing p53-R273H through binding to MDM2 and disrupting its association with mutant p53, while inhibition of VCP leads to ubiquitination and degradation of p53-R273H, promoting cell death. VCP may serve as a potential target for the development of pancreatic cancer therapy.
Editorial Material
Oncology
Qian Hao, Xiang Zhou
CANCER BIOLOGY & MEDICINE
(2022)
Article
Oncology
Tao Han, Jing Tong, Mengxin Wang, Yu Gan, Bo Gao, Jiaxiang Chen, Youxun Liu, Qian Hao, Xiang Zhou
Summary: Olaparib is a widely used PARP inhibitor in the treatment of solid tumors. Its anti-tumor activity is achieved through the inhibition of PARP enzymes and blocking DNA repair. This study reveals that Olaparib activates the nucleolar stress-RPs-p53 pathway, leading to the activation of p53 and the inhibition of cancer cell survival and proliferation.
FRONTIERS IN ONCOLOGY
(2022)
Review
Pharmacology & Pharmacy
Michelle J. Chen, Anne Gatignol, Robert J. Scarborough
Summary: This review examines the development of RNA technologies for treating HIV-1 infections over the past three decades, assessing their efficacy and safety. RNA-based therapies have the potential to be long-term and effective treatments for inhibiting HIV-1 through gene therapy.
EXPERT OPINION ON DRUG DISCOVERY
(2023)
Editorial Material
Cell Biology
Xiang Zhou, Ji Hoon Jung, Hua Lu
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Cell Biology
Qian Hao, Jiaxiang Chen, Hua Lu, Xiang Zhou
Summary: The tumor-suppressive activity of p53 is mainly due to its ability to induce cell death, specifically apoptosis, through various mechanisms. It transcriptionally activates pro-apoptotic genes and inhibits anti-apoptotic genes, leading to mitochondrial apoptosis. It also promotes mitochondrial apoptosis by directly interacting with BCL-2 family proteins in the mitochondria. ARTS, a pro-apoptotic protein encoded by an alternative spliced variant of the SEPT4 gene, facilitates BCL-2 and XIAP degradation, triggering apoptosis. ARTS is a new p53 target gene that enhances mitochondrial apoptosis by interacting with p53. This review discusses the mechanisms of p53-induced mitochondrial apoptosis, the role of ARTS in regulating mitochondrial cell death, and the clinical significance of ARTS in cancer and non-cancer diseases.
JOURNAL OF MOLECULAR CELL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Chen Xiong, Hong Ling, Qian Hao, Xiang Zhou
Summary: Cuproptosis is a newly identified form of copper-induced cell death that primarily affects cells relying on oxidative phosphorylation as their main energy source. This process involves copper binding to lipoylated proteins in the tricarboxylic acid cycle, leading to the aggregation of these proteins, destabilization of iron-sulfur cluster proteins, and proteotoxic stress. Cancer cells, on the other hand, predominantly utilize glycolysis and are resistant to cuproptosis. However, the tumor suppressor p53, which regulates metabolism, may have a role in cuproptosis regulation by influencing glycolysis and the biogenesis of iron-sulfur clusters and the copper chelator glutathione.
CELL DEATH AND DIFFERENTIATION
(2023)
Review
Cell Biology
Liping Guan, Qian Hao, Fenfen Shi, Bo Gao, Mengxin Wang, Xiang Zhou, Tao Han, Wenjie Ren
Summary: Circular RNA (circRNAs) is a circular non-coding RNA formed by back-splicing from precursor messenger RNA. It can be released and captured by other cell types, acting as connections between different cell types for signaling pathways. CircRNAs reshape the tumor microenvironment (TME) by regulating epithelial-stromal transformation, tumor vascularization, immune cell function, and inflammatory responses, playing a crucial role in cancer development.
CELL DEATH & DISEASE
(2023)
Article
Biochemistry & Molecular Biology
Yu Gan, Jun Deng, Qian Hao, Yingdan Huang, Tao Han, Jin-Guo Xu, Min Zhao, Litong Yao, Yingying Xu, Jianping Xiong, Hua Lu, Chunmeng Wang, Jiaxiang Chen, Xiang Zhou
Summary: In this study, it was found that UTP11 plays a crucial role in the biosynthesis of 18S ribosomal RNAs (rRNA) by binding to the pre-rRNA processing factor, MPP10. UTP11 is overexpressed in human cancers and is associated with poor prognoses. Depletion of UTP11 inhibits cancer cell growth through p53-dependent and -independent mechanisms, while UTP11 overexpression promotes cancer cell growth and progression. The study also reveals that UTP11 depletion triggers nucleolar stress and enhances ferroptosis, contributing to the inhibition of cancer cell survival and growth.
Article
Biochemistry & Molecular Biology
Litong Yao, Qian Hao, Mozhi Wang, Yuhai Chen, Hongyi Cao, Qiang Zhang, Keda Yu, Yizhou Jiang, Zhiming Shao, Xiang Zhou, Yingying Xu
Summary: In this study, researchers identified KLHL29 as a crucial tumor suppressor that regulates chemosensitivity in triple-negative breast cancer (TNBC). Low levels of KLHL29 were associated with unfavorable prognoses. Mechanistically, KLHL29 suppressed TNBC growth by degrading DDX3X and inhibiting cell cycle progression. The combination of DDX3X inhibitor RK33 and platinum-based chemotherapy showed promising results in suppressing TNBC.
Letter
Biology
Hanzhi Dong, Quan Liao, Bangxiang Xie, Yu-an Qiu, Zhiqiang Peng, Jun Deng, Jianping Xiong, Hua Lu, Qian Hao, Xiang Zhou
SCIENCE CHINA-LIFE SCIENCES
(2023)
Article
Medicine, General & Internal
Bangxiang Xie, Qian Hao, Xiang Zhou, Dexi Chen
Summary: The HBx protein of hepatitis B virus interacts with the TAp63 protein and inhibits its transcriptional activity, leading to the progression of hepatocellular carcinoma with defective p53.
CHINESE MEDICAL JOURNAL
(2022)