title: COMMD9 promotes TFDP1/E2F1 transcriptional activity via interaction with TFDP1 in non-small cell lung cancer.
abstract: COMMD protein family is an evolutionarily conserved gene family implicated in a number of critical processes including inflammation, copper homeostasis, sodium balance, endosomal sorting and cancer. In an effort to profile the expression pattern of COMMD family in several non-small cell lung cancer (NSCLC) cell lines, we found that compared with that in human bronchial epithelial (HBE) cells, the mRNA expression levels of five COMMD genes including COMMD3, COMMD4, COMMD5, COMMD6 and COMMD8 were significantly down-regulated, whereas COMMD9 was up-regulated in NSCLC cell lines. Here we reported that the expression of COMMD9 protein was significantly increased in various NSCLC cell lines and tissue samples. SiRNA-induced knocking down of COMMD9 inhibited proliferation and migration, arrested cell cycle at G1/S transition and induced autophagy in NSCLC cells. Mechanistically, COMMD9 interacted with the TFDP1 through COMM domain, and DNA-binding domain of TFDP1 was required for this interaction. Moreover, decreased expression COMMD9 attenuated TFDP1/E2F1 activation accompanied with enhanced p53 signaling pathway. Taken together, these findings demonstrate that COMMD9 participates in TFDP1/E2F1 activation and plays a critical role in non-small cell lung cancer.
authors.affiliation: Institute of Translation Medicine, Nanchang University, Nanchang City 330031, Jiangxi, China; School of Life Sciences, Nanchang University, Nanchang City 330031, Jiangxi, China.
authors.forename: Weihua
authors.initials: W
authors.lastname: Zhan
authors.affiliation: Institute of Translation Medicine, Nanchang University, Nanchang City 330031, Jiangxi, China.
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Wang
authors.affiliation: Institute of Translation Medicine, Nanchang University, Nanchang City 330031, Jiangxi, China; School of Life Sciences, Nanchang University, Nanchang City 330031, Jiangxi, China.
authors.forename: Tianyu
authors.initials: T
authors.lastname: Han
authors.affiliation: Institute of Translation Medicine, Nanchang University, Nanchang City 330031, Jiangxi, China.
authors.forename: Caifeng
authors.initials: C
authors.lastname: Xie
authors.affiliation: Research Institute of Applied Biology, Shanxi University, Taiyuan, Shanxi 030006, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Institute of Translation Medicine, Nanchang University, Nanchang City 330031, Jiangxi, China.
authors.forename: Mingxi
authors.initials: M
authors.lastname: Gan
authors.affiliation: Institute of Translation Medicine, Nanchang University, Nanchang City 330031, Jiangxi, China; School of Life Sciences, Nanchang University, Nanchang City 330031, Jiangxi, China. Electronic address: jianbinwang1@gmail.com.
authors.forename: Jian-Bin
authors.initials: JB
authors.lastname: Wang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D001343:Autophagy / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D002448:Cell Adhesion / Q000235:genetics; D059447:Cell Cycle Checkpoints / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D050687:E2F1 Transcription Factor / Q000235:genetics*; D016193:G1 Phase / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D011485:Protein Binding / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016196:S Phase / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D050680:Transcription Factor DP1 / Q000235:genetics*; D014158:Transcription, Genetic; D014410:Tumor Stem Cell Assay; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C000625142:COMMD9 protein, human; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D012333:RNA, Messenger; C493735:TFDP1 protein, human; D050680:Transcription Factor DP1; D016159:Tumor Suppressor Protein p53
keywords: COMMD9; Non-small cell lung cancer; TFDP1/E2F1; p53