CCAR2

Official Full Name

cell cycle and apoptosis regulator 2

Organism

Homo sapiens

Gene ID

57805

Background

Enables RNA polymerase II complex binding activity and enzyme inhibitor activity. Involved in several processes, including mitochondrial fragmentation involved in apoptotic process; regulation of primary metabolic process; and regulation of signal transduction. Located in several cellular components, including mitochondrial matrix; nucleoplasm; and spindle. Part of DBIRD complex. [provided by Alliance of Genome Resources, Feb 2025]

Synonyms

DBC1; DBC-1; NET35; p30DBC; p30 DBC; KIAA1967

Cat.No.	Product Name	Price
CSC-DC003140	Panoply™ Human CHRNB3 Knockdown Stable Cell Line	Inquiry
CSC-DC004040	Panoply™ Human DBC1 Knockdown Stable Cell Line	Inquiry
CSC-DC008164	Panoply™ Human KIAA1967 Knockdown Stable Cell Line	Inquiry
CSC-SC003140	Panoply™ Human CHRNB3 Over-expressing Stable Cell Line	Inquiry
CSC-SC004040	Panoply™ Human DBC1 Over-expressing Stable Cell Line	Inquiry
CSC-SC008164	Panoply™ Human KIAA1967 Over-expressing Stable Cell Line	Inquiry
CLOE-0168	Human CHRNB3(His) HEK293 Cell Lysate	Inquiry
CLOE-0172	Human CHRNB3(Fc) HEK293 Cell Lysate	Inquiry

Cat.No.	Product Name	Price
AD03722Z	Human CHRNB3 adenoviral particles	Inquiry
AD04598Z	Human DBC1 adenoviral particles	Inquiry
AD08631Z	Human KIAA1967 adenoviral particles	Inquiry
LV09021L	human CHRNB3 (NM_000749) lentivirus particles	Inquiry
LV10318L	human DBC1 (NM_014618) lentivirus particles	Inquiry
LV16281L	human KIAA1967 (NM_021174) lentivirus particles	Inquiry

Cat.No.	Product Name	Price
SHH274685	shRNA set against Human DBC1 (NM_014618.2)	Inquiry
SHG177499	shRNA set against Human CHRNB3(NM_000749.3)	Inquiry
SHG177595	shRNA set against Rat Chrnb3(NM_133597.1)	Inquiry
SHG222105	shRNA set against Mouse Dbc1(NM_019967.2)	Inquiry
SHG222113	shRNA set against Human DBC1(NM_014618.2)	Inquiry
SHH263645	shRNA set against Human CHRNB3 (NM_000749.3)	Inquiry
SHH263649	shRNA set against Mouse CHRNB3 (NM_173212.4)	Inquiry
SHH263653	shRNA set against Rat CHRNB3 (NM_133597.1)	Inquiry
SHH274689	shRNA set against Mouse DBC1 (NM_019967.2)	Inquiry
SHH274693	shRNA set against Rat DBC1 (NM_080482.2)	Inquiry
SHH324915	shRNA set against Human KIAA1967 (NM_021174.5)	Inquiry
SHW005318	shRNA set against Chicken CHRNB3 (NM_204812)	Inquiry

Cat.No.	Product Name	Price
OE-PNDC000301	Human CHRNB3 Nanodisc	Inquiry

Cat.No.	Product Name	Price
CDCB158217	Human CHRNB3 ORF clone (BC069681)	Inquiry
MiUTR1M-03695	DBC1 miRNA 3'UTR clone	Inquiry
MiUTR1H-02674	DBC1 miRNA 3'UTR clone	Inquiry
MiUTR1H-02149	CHRNB3 miRNA 3'UTR clone	Inquiry
CDFR014110	Rat Chrnb3 cDNA Clone(NM_133597.1)	Inquiry
MiUTR1R-00990	CHRNB3 miRNA 3'UTR clone	Inquiry
CDCR380840	Rat Dbc1 ORF Clone(NM_080482.2)	Inquiry
MiUTR3H-09172	KIAA1967 miRNA 3'UTR clone	Inquiry
CDCB159808	Human DBC1 ORF clone (BC021560)	Inquiry
CDCR337211	Human CHRNB3 ORF Clone(NM_000749.3)	Inquiry
CDCR260222	Mouse Chrnb3 ORF Clone(NM_027454.4)	Inquiry
CDCR254584	Mouse Dbc1 ORF Clone(NM_019967.2)	Inquiry
CDCS405878	Human CHRNB3 ORF Clone (BC069681)	Inquiry
CDCS405879	Human CHRNB3 ORF Clone (BC069703)	Inquiry
CDCS413711	Human DBC1 ORF Clone (BC021560)	Inquiry
CDCS415304	Human KIAA1967 ORF Clone (BC018269)	Inquiry
CDCB186206	Rabbit CCAR2 ORF clone (XM_002722413.2)	Inquiry
CDCB184381	Rabbit CHRNB3 ORF clone (XM_002720792.2)	Inquiry
CDCB166793	Chicken CHRNB3 ORF Clone (NM_204812)	Inquiry
CDCR272080	Mouse Chrnb3 ORF Clone(NM_173212.4)	Inquiry
CDCR381165	Rat Chrnb3 ORF Clone(NM_133597.1)	Inquiry

Detailed Information

Recent Research Progress

The cell cycle and apoptosis regulator 2 [CCAR2, formerly known as DBC1 (deleted in breast cancer 1)] is a multifaceted protein that regulates multiple subsets of cellular functions. CCAR2 controls transcription, mRNA splicing, DNA damage response, circadian rhythm, inflammation, metabolism, differentiation, proliferation, survival and apoptosis. Regarding cancer growth, CCAR2 is thought to act as a tumor promoter or tumor suppressor depending on the background.

CCAR2 and cervical cancer

Wootae Kim et al. found that cytokine and chemokine production by CCAR2-deficient cells increased under oxidative conditions. In particular, H₂O₂-treated CCAR2-depleted cells showed a significant increase in interleukin-8 (IL-8) production, indicating a negative regulation of IL-8 by CCAR2. Up-regulation of IL-8 expression in CCAR2-deficient cells occured by activation of the transcription factor AP-1. A negative correlation between CCAR2 and IL-8 expression was confirmed by examining mRNA and protein levels in tissues of patients with cervical cancer. Furthermore, CCAR2-regulated IL-8 expression is associated with shorter survival in patients with cervical cancer. Overall, the data suggest that CCAR2 plays a key role in controlling cancer secretory proteome and cancer progression.

CCAR2 and SCC

High expression of CCAR2 has been reported to be associated with poor outcomes of squamous cell carcinoma (SCC). Recent studies have found that CCAR2 is highly overexpressed in p53-deficient SCC cell lines compared with normal primary keratinocytes due to increased protein stability. The role of CCAR2 in promoting the stability of the transcription factors the regulatory factor X (RFX1) and cAMP responsive element binding protein 1 (CREB1) has been determined, and these are necessary for proliferation. The results of the study indicated that CCAR2 is required for in vitro proliferation and established SCC tumors in vivo. These findings suggest an important role for CCAR2 in maintaining cell cycle progression and promoting SCC tumorigenesis.

CCAR2 and gastric carcinoma

Gastric cancer (GC) is one of the most common cancers and the second most common cause of cancer death. Recently, studies have shown that the expression of CK2a and pCCAR2 increases with the progression of GC, and the expression status of CK2a and pCCAR2 in GC are indicator of poor prognosis in GC patients. In particular, blocking the CK2a-CCAR2 pathway reduced proliferation and invasion of GC cells. In addition, the study demonstrates that CK2a phosphorylates CCAR2, which is closely related to EMT in GC cells. Therefore, studies have shown that the CK2a-CCAR2 pathway may be a new therapeutic target for the treatment of GC.

CCAR2 and OS

Osteosarcoma (OS) is the most common primary malignant bone tumor. Recently, studies have shown that the expression of CCAR2 and AR can be used as a prognostic indicator of OS. Immunohistochemical expression of CCAR2 and the androgen receptor (AR) was significantly associated with higher clinical stage and higher histological grade, and predicted shorter survival rates. Especially, CCAR2 expression was an independent prognostic indicator of overall survival and recurrence-free survival by multivariate analysis. In the OS cell lines U2OS and SaOS2, knockdown of CCAR2 and AR with siRNA significantly reduced cell proliferation and inhibited proliferation-related signaling. In addition, knockdown of CCAR2 and AR reduced the invasive activity and inhibited invasion-related signaling of OS cells. Interestingly, CCAR2 affects the stabilization of AR proteins through a mechanism involving AR ubiquitination. Proteasome-mediated degradation and poly-ubiquitination of AR increase with the knockdown of CCAR2. In conclusion, this study demonstrates that CCAR2 is involved in the stabilization of AR proteins, and that the CCAR2-AR pathway may be involved in the progression of OS.

CCAR2 and HCC

Hepatocellular carcinoma (HCC) is one of the most common human malignancies and usually develops in chronic liver disease. Recent studies have found that CCAR2 protein may be a prognostic marker for shorter RFS in hepatitis virus-associated HCC patients and human hepatocarcinogenesis was a multistep process accompanied by a stepwise increase in high CCAR2 expression from LGDN, through HGDN, to HCC. Patients with high CCAR2 expression can be considered candidates for adjuvant therapy after hepatectomy.

CCAR2 and CRC

Abnormal activation of the Wnt/β-catenin pathway contributes to the progression of colorectal cancer (CRC). CCAR2 has recently been reported as a negative regulator of SIRT1 and transcriptional coactivators for the regulation of Wnt/β-catenin signaling. It was identified the genome-wide targets of CCAR2 and found that loss of CCAR2 inhibits the expression of β-catenin target genes including PROX1, a transcription factor linked to CRC progression. In mechanism, CCAR2 stabilizes LEF1-β-catenin interaction by inhibiting SIRT1-mediated beta-catenin deacetylation, thereby enhancing LEX1-β-catenin complex formation and long-range chromatin loop at the PROX1 locus Chemical. In addition, CCAR2 is also required for transcriptional activity of PROX1, suggesting that CCAR2 has a dual function in regulating the β-catenin-PROX1 signaling axis: as a coactivator of β-catenin and PROX1. Importantly, deletion of CCAR2 inhibited the growth and tumorigenic potential of colon cancer cells, and CCAR2 expression orrelated with recurrence-free survival in patients with advanced CRC. The results identified CCAR2 as a key positive regulator of the β-catenin-PROX1 signaling axis and a key factor in β-catenin-PROX1-mediated CRC progression.

In summary, there is increasing evidence that CCAR2 is closely related to a variety of cancers. Therefore, further study of the function of CCAR2 and its important role in the mechanism of cancer development will provide new insights into the diagnosis and treatment of related cancers.

References:

Wootae Kim, et al. CCAR2 negatively regulates IL-8 production in cervical cancer cells. Oncotarget, 2018, 9(1): 1143-1155
SA Best, et al. CCAR2 Is Required for Proliferation and Tumor Maintenance in Human Squamous Cell Carcinoma. Journal of Investigative Dermatology, 2017, 137: 506e512
Huan YW, et al. DBC1 promotes anoikis resistance of gastric cancer cells by regulating NF-κB activity. Oncology Reports, 2015, 34: 843-849
Jun Sang Bae, et al. CK2a phosphorylates DBC1 and is involved in the progression of gastric carcinoma and predicts poor survival of gastric carcinoma patients. International Journal of Cancer, 2015, 136: 797–809
Sajeev Wagle, et al. DBC1/CCAR2 is involved in the stabilization of androgen receptor and the progression of osteosarcoma. Scientific Reports, 2015, 5: 13144
Sang Yun Ha, et al. Expression of DBC1 is associated with poor prognosis in hepatitis virus-related hepatocellular carcinoma. Pathology – Research and Practice, 2016, 212: 616–621
Yu EJ, et al. Positive regulation of β-catenin–PROX1 signaling axis by DBC1 in colon cancer progression. Oncogene, 2016, 35: 3410–3418

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