title: CBX3 promotes colon cancer cell proliferation by CDK6 kinase-independent function during cell cycle.
abstract: Heterochromatin protein 1γ (CBX3) links histone methylation marks to transcriptional silence, DNA repair and RNA splicing, but a role for CBX3 in cancer remains largely unknown. In this study, we show that CBX3 in colon cancer cells promotes the progression of the cell cycle and proliferation in vitro and in vivo. Cell cycle (G1 phase to S phase) related gene CDK6 and p21 were further identified as targets of CBX3. In addition, we found that enhancing CDK6 suppresses cell proliferation by upregulating inhibitor p21 in the absence of CBX3, and this function is independent of the kinase activity of CDK6. Our results demonstrate a key role of CBX3 in colon carcinogenesis via suppressing the expression of CDK6/p21, which may disrupt the role of CDK6 in transcriptionally regulating p21, as part of a negative feedback loop to limit CDK6 excessive activation.
authors.affiliation: Chongqing Key Laboratory of Department of General Surgery, Chongqing Medical University, Chongqing, China.|Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Fan
authors.affiliation: Chongqing Key Laboratory of Department of General Surgery, Chongqing Medical University, Chongqing, China.|Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Haiping
authors.initials: H
authors.lastname: Li
authors.affiliation: Chongqing Key Laboratory of Department of General Surgery, Chongqing Medical University, Chongqing, China.|Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Liang
authors.affiliation: Chongqing Key Laboratory of Department of General Surgery, Chongqing Medical University, Chongqing, China.|Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Xiang
mesh_terms: D000818:Animals; D064113:CRISPR-Cas Systems; D002453:Cell Cycle / Q000235:genetics*; D049109:Cell Proliferation / Q000235:genetics*; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics* / Q000378:metabolism; D003110:Colonic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051361:Cyclin-Dependent Kinase 6 / Q000235:genetics* / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D008819:Mice, Nude; D008856:Microscopy, Fluorescence; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014183:Transplantation, Heterologous; D047368:Tumor Burden / Q000235:genetics
chemical_list: C518294:CBX3 protein, human; C493956:CDKN1A protein, human; D002868:Chromosomal Proteins, Non-Histone; D050759:Cyclin-Dependent Kinase Inhibitor p21; C495911:CDK6 protein, human; D051361:Cyclin-Dependent Kinase 6
keywords: CBX3; CDK6; colon cancer; p21; proliferation