Network biology of tumor stem-like cells identified a regulatory role of CBX5 in lung cancer.
Mounting evidence links cancers possessing stem-like properties with worse prognosis. Network biology with signal processing mechanics was explored here using expression profiles of a panel of tumor stem-like cells (TSLCs). The profiles were compared to their parental tumor cells (PTCs) and the human embryonic stem cells (hESCs), for the identification of gene chromobox homolog 5, CBX5, as a potential target for lung cancer. CBX5 was found to regulate the stem-like properties of lung TSLCs and was predictive of lung cancer prognosis. The investigation was facilitated by finding target genes based on modeling epistatic signaling mechanics via a predictive and scalable network-based survival model. Topologically-weighted measurements of CBX5 were synchronized with those of BIRC5, DNMT1, E2F1, ESR1, MLH1, MSH2, RB1, SMAD1 and TAF5. We validated our findings in another Taiwanese lung cancer cohort, as well as in knockdown experiments using sh-CBX5 RNAi both in vitro and in vivo.
Institute of Oral Biology, National Yang-Ming University, Taipei, Taiwan. yauhuayu@gmail.com
Yau-Hua
YH
Yu
Guang-Yuh
GY
Chiou
Pin-I
PI
Huang
Wen-Liang
WL
Lo
Chien-Ying
CY
Wang
Kai-Hsi
KH
Lu
Cheng-Chia
CC
Yu
Gil
G
Alterovitz
Wen-Chien
WC
Huang
Jeng-Fan
JF
Lo
Han-Shui
HS
Hsu
Shih-Hwa
SH
Chiou
D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D000090266:Chromobox Protein Homolog 5; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D018450:Disease Progression; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016130:Immunophenotyping; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D058977:Molecular Sequence Annotation; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D034622:RNA Interference; D015203:Reproducibility of Results; D015398:Signal Transduction; D014158:Transcription, Genetic
C000715594:CBX5 protein, human; C000715595:CBX5 protein, mouse; D002868:Chromosomal Proteins, Non-Histone; D000090266:Chromobox Protein Homolog 5