BNIP3 Upregulation Characterizes Cancer Cell Subpopulation With Increased Fitness and Proliferation

被引:7
作者
Zhu, Yanyan [1 ]
Chen, Bowang [2 ,3 ]
Yan, Junya [1 ]
Zhao, Wendi [4 ]
Dou, Pengli [5 ]
Sun, Na [2 ]
Wang, Yaokai [6 ]
Huang, Xiaoyun [2 ,3 ]
机构
[1] Zhengzhou Univ, Peoples Hosp, Henan Prov Peoples Hosp, Sch Clin Med,Dept Oncol, Zhengzhou, Peoples R China
[2] Intelliphecy, Dept Computat Oncol, Shenzhen, Peoples R China
[3] Intelliphecy, Ctr Syst Biol, Shenzhen, Peoples R China
[4] Henan Univ, Henan Prov Peoples Hosp, Sch Clin Med, Dept Oncol, Zhengzhou, Peoples R China
[5] Intelliphecy, Dept Expt Canc Modeling, Nanjing, Peoples R China
[6] Univ Hong Kong, Shenzhen Hosp, Dept Gynecol & Obstet, Shenzhen, Peoples R China
来源
FRONTIERS IN ONCOLOGY | 2022年 / 12卷
基金
美国国家科学基金会;
关键词
BNIP3; ScRNA-seq; mitophagy; systems biology; cancer heterogeneity; SINGLE-CELL; BREAST-CANCER; HYPOXIA; AUTOPHAGY; PROGRESSION; MITOPHAGY; CARCINOMA; DYNAMICS; GENE;
D O I
10.3389/fonc.2022.923890
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
BNIP3 is a BH3-only protein with both pro-apoptotic and pro-survival roles depending on the cellular context. It remains unclear how BNIP3 RNA level dictates cell fate decisions of cancer cells. Here, we undertook a quantitative analysis of BNIP3 expression and functions in single-cell datasets of various epithelial malignancies. Our results demonstrated that BNIP3 upregulation characterizes cancer cell subpopulations with increased fitness and proliferation. We further validated the upregulation of BNIP3 in liver cancer 3D organoid cultures compared with 2D culture. Taken together, the combination of in silico perturbations using public single-cell datasets and experimental cancer modeling using organoids ushered in a new approach to address cancer heterogeneity.
引用
收藏
页数:9
相关论文
共 35 条
[1]  
Aibar S, 2017, NAT METHODS, V14, P1083, DOI [10.1038/NMETH.4463, 10.1038/nmeth.4463]
[2]   A human liver cell atlas reveals heterogeneity and epithelial progenitors [J].
Aizarani, Nadim ;
Saviano, Antonio ;
Sagar ;
Mailly, Laurent ;
Durand, Sarah ;
Herman, Josip S. ;
Pessaux, Patrick ;
Baumert, Thomas F. ;
Gruen, Dominic .
NATURE, 2019, 572 (7768) :199-204
[3]   Chemical Proteomics Identifies Druggable Vulnerabilities in a Genetically Defined Cancer [J].
Bar-Peled, Liron ;
Kemper, Esther K. ;
Suciu, Radu M. ;
Vinogradova, Ekaterina V. ;
Backus, Keriann M. ;
Horning, Benjamin D. ;
Paul, Thomas A. ;
Ichu, Taka-Aki ;
Svensson, Robert U. ;
Olucha, Jose ;
Chang, Max W. ;
Kok, Bernard P. ;
Zhu, Zhou ;
Ihle, Nathan T. ;
Dix, Melissa M. ;
Jiang, Ping ;
Hayward, Matthew M. ;
Saez, Enrique ;
Shaw, Reuben J. ;
Cravatt, Benjamin F. .
CELL, 2017, 171 (03) :696-+
[4]   BNIP3 subfamily BH3-only proteins: mitochondrial stress sensors in normal and pathological functions [J].
Chinnadurai, G. ;
Vijayalingam, S. ;
Gibson, S. B. .
ONCOGENE, 2008, 27 (Suppl 1) :S114-S127
[5]   Mitophagy defects arising from BNip3 loss promote mammary tumor progression to metastasis [J].
Chourasia, Aparajita H. ;
Tracy, Kristin ;
Frankenberger, Casey ;
Boland, Michelle L. ;
Sharifi, Marina N. ;
Drake, Lauren E. ;
Sachleben, Joseph R. ;
Asara, John M. ;
Locasale, Jason W. ;
Karczmar, Gregory S. ;
Macleod, Kay F. .
EMBO REPORTS, 2015, 16 (09) :1145-1163
[6]   Tumour Hypoxia Affects the Responsiveness of Cancer Cells to Chemotherapy and Promotes Cancer Progression [J].
Cosse, Jean-Philippe ;
Michiels, Carine .
ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY, 2008, 8 (07) :790-797
[7]   BNIP3 protects HepG2 cells against etoposide-induced cell death under hypoxia by an autophagy-independent pathway [J].
Cosse, Jean-Philippe ;
Rommelaere, Guillaume ;
Ninane, Noelle ;
Arnould, Thierry ;
Michiels, Carine .
BIOCHEMICAL PHARMACOLOGY, 2010, 80 (08) :1160-1169
[8]   Tumor Functional Heterogeneity Unraveled by scRNA-seq Technologies [J].
Gonzalez-Silva, Laura ;
Quevedo, Laura ;
Varela, Ignacio .
TRENDS IN CANCER, 2020, 6 (01) :13-19
[9]   GSVA: gene set variation analysis for microarray and RNA-Seq data [J].
Haenzelmann, Sonja ;
Castelo, Robert ;
Guinney, Justin .
BMC BIOINFORMATICS, 2013, 14
[10]   TRRUST v2: an expanded reference database of human and mouse transcriptional regulatory interactions [J].
Han, Heonjong ;
Cho, Jae-Won ;
Lee, Sangyoung ;
Yun, Ayoung ;
Kim, Hyojin ;
Bae, Dasom ;
Yang, Sunmo ;
Kim, Chan Yeong ;
Lee, Muyoung ;
Kim, Eunbeen ;
Lee, Sungho ;
Kang, Byunghee ;
Jeong, Dabin ;
Kim, Yaeji ;
Jeon, Hyeon-Nae ;
Jung, Haein ;
Nam, Sunhwee ;
Chung, Michael ;
Kim, Jong-Hoon ;
Lee, Insuk .
NUCLEIC ACIDS RESEARCH, 2018, 46 (D1) :D380-D386