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Emerging roles of JMJD3 in cancer
Maryam Farzaneh1,2, Zeinab Kuchaki3, Fatima Rashid Sheykhahmad4
1Fertility, Infertility and Perinatology Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. Maryamfarzaneh2013@yahoo.com.
Abstract:
Histone lysine methylation plays a key role in gene activation and repression. The trimethylation of histone H3 on lysine-27 (H3K27me3) is a critical epigenetic event that is controlled by Jumonji domain-containing protein-3 (JMJD3). JMJD3 is a histone demethylase that specifically removes methyl groups. Previous studies have suggested that JMJD3 has a dual role in cancer cells. JMJD3 stimulates the expression of proliferative-related genes and increases tumor cell growth, propagation, and migration in various cancers, including neural, prostate, ovary, skin, esophagus, leukemia, hepatic, head and neck, renal, lymphoma, and lung. In contrast, JMJD3 can suppress the propagation of tumor cells, and enhance their apoptosis in colorectal, breast, and pancreatic cancers. In this review, we summarized the recent advances of JMJD3 function in cancer cells.
Insights
Jumonji domain-containing protein-3 (JMJD3) has a dual role in cancer, promoting growth in some cancers while inhibiting it in others. This review summarizes JMJD3
Area of Science:
- Epigenetics
- Molecular Biology
- Cancer Research
Background:
- Histone lysine methylation, specifically histone H3 trimethylation on lysine-27 (H3K27me3), is a crucial epigenetic mechanism regulating gene expression.
- Jumonji domain-containing protein-3 (JMJD3) is a key histone demethylase responsible for removing methyl groups, thereby influencing H3K27me3 levels.
- JMJD3's role in cancer is complex, with evidence suggesting both oncogenic and tumor-suppressive functions across different cancer types.
Purpose of the Study:
- To review and synthesize recent findings on the multifaceted roles of JMJD3 in various cancer cells.
- To highlight the contrasting effects of JMJD3 on tumor growth, migration, and apoptosis in different malignancies.
- To provide a comprehensive overview of JMJD3's impact on cancer progression and potential therapeutic implications.
Main Methods:
- Literature review of recent scientific publications.
- Analysis of studies investigating JMJD3's enzymatic activity and its downstream effects on gene expression.
- Compilation of data from preclinical and clinical studies examining JMJD3's role in different cancer types.
Main Results:
- JMJD3 promotes proliferation, migration, and growth in cancers such as neural, prostate, ovarian, skin, esophageal, leukemia, hepatic, head and neck, renal, lymphoma, and lung cancers.
- Conversely, JMJD3 has been shown to suppress tumor propagation and enhance apoptosis in colorectal, breast, and pancreatic cancers.
- The dual role of JMJD3 appears to be context-dependent, influenced by the specific cancer type and cellular environment.
Conclusions:
- JMJD3 exhibits a dichotomous function in cancer, acting as an oncoprotein in some contexts and a tumor suppressor in others.
- Understanding the precise mechanisms underlying JMJD3's opposing roles is critical for developing targeted cancer therapies.
- Further research into JMJD3's regulatory pathways and interactions may unlock new therapeutic strategies for a wide range of cancers.
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