CCND1

Official Full Name

cyclin D1

Organism

Homo sapiens

GeneID

595

Background

The protein encoded by this gene belongs to the highly conserved cyclin family, whose members are characterized by a dramatic periodicity in protein abundance throughout the cell cycle. Cyclins function as regulators of CDK kinases. Different cyclins exhibit distinct expression and degradation patterns which contribute to the temporal coordination of each mitotic event. This cyclin forms a complex with and functions as a regulatory subunit of CDK4 or CDK6, whose activity is required for cell cycle G1/S transition. This protein has been shown to interact with tumor suppressor protein Rb and the expression of this gene is regulated positively by Rb. Mutations, amplification and overexpression of this gene, which alters cell cycle progression, are observed frequently in a variety of human cancers. [provided by RefSeq, Dec 2019]

Synonyms

BCL1; PRAD1; U21B31; D11S287E;

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Detailed Information

Recent Research Progress

Cyclin D1 (encoded by the CCND1 gene) is a G1 cyclin that is important for regulating the transition of G1 to S (G1-S) in different cell types. By cooperating with its binding partners CDK4 and CDK6, CCND1 promotes phosphorylation of retinoblastoma proteins, resulting in activation of the E2F transcription factor; thus, the cell cycle is passed through G1 into the S phase. Overexpression of CCND1 is commonly observed in various types of human cancers, including HCC, and serves a critical role in the initiation of carcinogenesis. CCND1 is also involved in abnormal cell growth processes, angiogenesis and resistance to apoptosis, making it a potential therapeutic target for tumor growth.

CCND1 and T-cell lymphoma

Adult T-cell lymphoma is a highly invasive T-cell malignancy. The study found that CCND1 levels were significantly elevated compared to adjacent non-tumor tissues, and miR-373 levels were significantly reduced in T-cell lymphoma tissues. Moreover, low miR-373 levels were associated with poor patient survival. Overexpression of miR-373 significantly inhibited cell growth, while consumption of miR-373 increased cell growth in T cell lymphoma cells. Furthermore, the effect of miR-373 on cell growth appeared to be caused by changes in cell proliferation. Finally, miR-373 was found to bind to the 3'-UTR of CCND1 mRNA to inhibit its translation in T cell lymphoma cells. In conclusion, a decrease in miR-373 levels in T-cell lymphoma tissue may contribute to the growth of T-cell lymphoma by CCND1-mediated cell proliferation.

CCND1 and CRC

Colorectal cancer (CRC) is one of the most common malignant gastrointestinal cancers, and its morbidity and mortality are on the rise. MicroRNA-374a (miR-374a) exhibits carcinogenic function in various tumor types. MiR-374a acts as a tumor suppressor by inactivating PI3K/AKT signaling and downstream signaling. This negative regulation was achieved by directly reducing CCND1 to inhibit proliferation, invasion and migration in colon cancer cells (Fig. 1). Furthermore, high miR-374a and low CCND1 expression in patient samples correlated with favorable outcomes, suggesting that miR-374a and CCND1 may be useful prognostic biomarkers.

Figure 1. Potential signaling pathway utilized by miR-374a to suppress proliferation, invasion and migration in colon cancer. (Qin AC, et al, Biochemical and Biophysical Research Communications, 2015)

CCND1 and OS

Metastasis is the leading cause of death in patients with osteosarcoma (OS). Overexpression of miR-195 has been reported to substantially inhibit the migration and invasion of OS cells in vitro and the formation of lung metastases in vivo. At the same time, CCND1 was identified as a target gene of miR-195 and further studied. Studies have indicated that low expression of miR-195 or high CCND1 was associated with positive overall survival and their expression inverse relate to each other. In conclusion, miR195 acts by down-regulating CCND1 as a tumor metastasis suppressor gene and can be used as a potential target for the treatment of OS.

CCND1 and HCC

The long non-coding RNA, homeobox transcript antisense RNA (Hotair), has been shown to play an important role in the regulation of various biological processes in hepatocellular carcinoma (HCC). Knockdown of HOTAIR expression by RNA interference inhibited cell proliferation and induces G0/G1 cell cycle arrest in Huh7 hepatocyte cancer cells. In addition, the expression levels of CCND1 mRNA and its CCND1 protein product were decreased in Huh7 cells after HOTAIR knockdown. Knockdown of HOTAIR reduced expression of phosphorylation signal transducer and activator of transcription 3 (STAT3), and binding of HOTAIR knockdown to STAT3 inhibition resulted in an additional decrease in CCND1 expression. The present studies have shown that Hotair may play a key role in the proliferation of liver cancer by regulating cell cycle, STAT3 activity and CCND1 expression. Therefore, Hotair may be a new potential therapeutic target for HCC therapy.

In conclusion, amplification and overexpression of CCND1 is frequently observed in a variety of tumors, which alters cell cycle progression. Therefore, further study of the mechanism of CCND1 in various cancers will provide new insights and new targets for the diagnosis and treatment of cancer.

References:

Tian YY, et al. Restoration of microRNA-373 suppresses growth of human T-cell lymphoma cells by repressing CCND1. European Review For Medical And Pharmacological Sciences, 20(21): 4435-4444
Su CL, et al. JARID2 inhibits leukemia cell proliferation by regulating CCND1 expression. International Journal Of Hematology, 2015, 102:76–85
Qin AC, et al. Inhibition of STAT3/cyclinD1 pathway promotes chemotherapeutic sensitivity of colorectal cancer. Biochemical and Biophysical Research Communications, 2015, 457: 681e687
Han K, et al. MicroRNA profiling identifies MiR-195 suppresses osteosarcoma cell metastasis by targeting CCND1. 2015, Oncotarget, 6(11): 8875-8889
Zhou JJ, et al. Knockdown of Hotair suppresses proliferation and cell cycle progression in hepatocellular carcinoma cell by downregulating CCND1 expression. Molecular Medicine Reports, 2017, 16: 4980-4986

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