Network biology of tumor stem-like cells identified a regulatory role of cbx5 in lung cancer

Yau Hua Yu*, Guang-Yuh Chiou, Pin I. Huang, Wen Liang Lo, Chien Ying Wang, Kai Hsi Lu, Cheng Chia Yu, Gil Alterovitz, Wen Chien Huang, Jeng Fan Lo, Han Shui Hsu, Shih Hwa Chiou

*Corresponding author for this work

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

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.

Original languageEnglish
Article number584
JournalScientific reports
Volume2
DOIs
StatePublished - 17 Sep 2012

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