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.

Diverse CBX family members as potential prognostic biomarkers in non‐small‐cell lung cancer

“…In this study, we investigated the upstream miRNA and TFs that regulate CBX3 mRNA expression and the target genes of CBX3. Also, several upstream and target genes of CBX3 had been proved in cancer [21,22]. The mechanism of gene dysregulation in NSCLC is complex.…”

CBX3/HP1γ is upregulated in tongue squamous cell carcinoma and is associated with an unfavorable prognosis

“…Among them, H3K9/HP1 is one of the key epigenetic silencing pathways for gene regulation ( 29 ). As an isoforms of HP1, CBX3/HP1γ has been proved to have various biological functions including RNA alternative splicing, DNA damage response, transcription elongation, cell growth and differentiation ( 7 ). Notably, highly elevated expression had been found in non-small cell lung cancer, prostate cancer and colorectal cancer ( 9 , 11 , 25 ) etc.…”

“…Increasing evidence had uncovered that CBX3/HP1γ was critically involved in tumorigenesis by promoting cell proliferation via regulating the expression of P21 or cyclin dependent kinases 6 (CDK6) during cell cycle ( 7 , 25 ). In addition, CBX3/HP1γ was demonstrated to have novel function in the epigenetic regulation of both cell differentiation and cancer development in various types of cancers ( 10 ).…”

“…HP1γ, encoded by the CBX3, is a paralog of HP1. By binding methylated H3K9, CBX3/HP1γ can recruit lots of cofactors which perform various biological functions including RNA alternative splicing, DNA damage response, transcription elongation, cell growth and differentiation ( 7 ). Moreover, CBX3/HP1γ is also located in euchromatin areas, which suggest that it may be also associated wih transcriptional activation ( 8 ).…”

Circular RNA hsa_circ_000984 promotes colon cancer growth and metastasis by sponging miR-106b

“…The well-known cyclin dependent kinases (CDKs) play essential role in the cell cycle regulation. Dysregulated activation of the CDK4/6 kinases is a hallmark of a variety of carcinomas [ 27 , 46 ]. Alterations of CDK6 expression have been well documented in bladder cancer and colorectal cancer tissues, respectively [ 26 , 47 ].…”