Abstract A181: High TOP2A inhibitive functions and mechanisms in human hepatocellular carcinoma (HCC)

Abstract

Abstract In order to study high TOP2A feedback-inhibitive morphogenesis mechanism in HCC, high TOP2A feedback-inhibitive multidimensional molecular network was constructed from mutual positive correlation of the overlapping with high TOP2A direct repressive relationship by GRNInfer and Pearson correlation coefficient CC ≤-0.25 in HCC (GSE10140-10141 from United States and Europe samples). Our result showed a loop from CBX5 to HOXA5 to NKX2_5, respectively; There are interactions among CBX5 to HOXA5 to NKX2_5, respectively. Therefore, we proposed high TOP2A feedback-inhibitive CBX5 interactive HOXA5 interactive NKX2_5 loop. Based on GO, KEGG, GenMAPP, BioCarta and disease databases, CBX5, HOXA5, NKX2_5 knowledge included embryonic skeletal morphogenesis, nucleus, chromatin assembly or disassembly, transcription factor activity, sequence-specific DNA-binding, thyroid gland development, etc. We further put forward high TOP2A feedback-inhibitive morphogenesis in HCC. In order to study high TOP2A inhibited-upstream neuroendocrine mechanism in HCC, high TOP2A inhibited-upstream multidimensional molecular network was constructed from mutual positive correlation of the overlapping with high TOP2A direct repressive relationship by GRNInfer and Pearson correlation coefficient CC ≤-0.25 in HCC (GSE10140-10141 from United States and Europe samples). Our result showed TOP2A inhibition by upstream RIMS3. Therefore, we proposed high TOP2A inhibited-upstream RIMS3. Based on GO, KEGG, GenMAPP, BioCarta and disease databases, RIMS3 knowledge included synapse, neurotransmitter transport, exocytosis, endocrine and CNS, secretory pathway, etc. We further put forward high TOP2A inhibited-upstream neuroendocrine in HCC. In order to study high TOP2A inside-out inhibiting-downstream growth mechanism in HCC, high TOP2A inside-out inhibiting-downstream multidimensional molecular network was constructed from mutual positive correlation of the overlapping with high TOP2A direct repressive relationship by GRNInfer and Pearson correlation coefficient CC ≤-0.25 in HCC (GSE10140-10141 from United States and Europe samples). Our result showed no direct relationship between TBL3 and SSTR5; There is a common NINJ2 activation by TBL3 and SSTR5. Therefore, we proposed high TOP2A inside-out inhibiting-downstream two ways TBL3 or SSTR5 common-shared NINJ2. Based on GO, KEGG, GenMAPP, BioCarta and disease databases, TBL3, SSTR5, NINJ2 knowledge included growth, integral to plasma membrane, G-protein signaling, negative regulation of cell proliferation, peptide receptor activity, second-messenger-mediated signaling, etc. We further put forward high TOP2A inside-out inhibiting-downstream growth in HCC. High TOP2A feedback-inhibitive, inhibited-upstream and inside-out inhibiting-downstream molecular networks were reverse-verified by the corresponding high TOP2A activatory network in HCC, activatory and repressive in no-tumor hepatitis/cirrhotic tissues (HBV or HCV infection), respectively. Citation Format: Lin Wang, Juxiang Huang, Minghu Jiang, Qingchun Chen, Zhenfu Jiang, Haitao Feng. High TOP2A inhibitive functions and mechanisms in human hepatocellular carcinoma (HCC). [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr A181.