JADE3

Official Full Name

jade family PHD finger 3

Organism

Homo sapiens

GeneID

9767

Background

This gene encodes a member of a family of large proteins containing PHD (plant homeo domain)-type zinc fingers. The encoded protein may be associated in a nuclear complex that functions in histone H4 acetylation. Alternative splicing results in multiple transcript variants encoding the same protein. [provided by RefSeq, Aug 2013]

Synonyms

PHF16; JADE-3;

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Detailed Information

Recent Research Progress

JADE3 (Jade family PHD finger 3) is a member of the small JADE family which also includes JADE1 and JADE2. Amino acid sequences of all JADEs present a high degree of identity in the N-terminal and PHD finger domain regions but are variable in their C-terminal fragments. JADE3 is localized both in nucleus and cytoplasm. JADE3 plays a role in inducing histone acetylation during transcription, and is involved in the progression of several human cancers.

JADE3 is markedly up-regulated and associated with poor prognosis in colon cancer

It has been shown that both mRNA and protein levels of JADE3 were markedly up regulated in colon cancer tissues and significantly correlated with cancer progression, and predicted shorter patient survival. Furthermore, JADE3 was expressed much higher in colon cancer cell lines that are enriched with a stem-like signature. Over-expression of JADE3 increased, while silencing JADE3 reduced cancer stem cell-like traits in colon cancer cells in vitro and in vivo. Importantly, silencing of JADE3 strongly impaired the tumor initiating capacity of coloncancer cells in vivo. In contrast, JADE1 and JADE2 did not show significant differences in tumor colon tissues and normal tissues.

JADE3 enhanced self-renewal capacity and tumorigenicity in colon cancer

In fact, among JADE1-3 family members, only JADE3 showed significant up-regulation in colon cancer and correlation with cancer stem cell(CSC) signature. Furthermore, one report showed that down-regulation of JADE3 significantly decreased the tumor initiating cell (TIC) frequency. Thus, the results indicate that JADE3 plays an important role in colon cancer initiation in vivo.

JADE3 interacted with the promoters of LGR5 and enhanced its transcriptional activity

One study reported that JADE3 can interact with the promoters of colon stem cell marker LGR5 and activate its transcription, by increasing the occupancy of p300 acetyl transferase and histone acetylation on the promoters. LGR5 was abrogated by silencing of JADE3. This indicates thatJADE3 might be an effective therapeutic target for the treatment of colon cancer.

Ectopic expression of JADE3 was induced by the Wnt/β-catenin signaling

One report showed that Wnt/β-catenin signaling-induced up regulation of JADE3 interacts with the promoters of LGR5, and further increases the enrichment ofp300 and histone acetylation in the promoters, in turn induces LGR5 over-expression, leading to increased CSCs properties in colon cancer (Figure 1).

Figure 1. Proposed model. Wnt/β-catenin signaling-induced up regulation of JADE3 interacts with the promoters of LGR5, and further increases the enrichment of p300 and histone acetylation in the promoters, in turn induces LGR5 over-expression, leading to increased CSCs properties in colon cancer.

References:

Jian Y, et al. Jade family PHD finger 3 (JADE3) increases cancer stem cell-like properties and tumorigenicity in colon cancer. Cancer Letters, 2018.
Panchenko M V. Structure, function and regulation of Jade Family PHD Finger 1 (JADE1). Gene, 2016, 589(1):1-11.

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