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HOTAIR: an oncogenic long non-coding RNA in different cancers.

Hajjari M, Salavaty A - Cancer Biol Med (2015)

Bottom Line: Instead, lncRNAs are involved in different regulatory processes, such as regulation of gene expression.Different lncRNAs exist throughout the genome.This RNA takes part in epigenetic regulation of genes and plays an important role in different cellular pathways by interacting with Polycomb Repressive Complex 2 (PRC2).

View Article: PubMed Central - PubMed

Affiliation: Department of Genetics, Faculty of Science, Shahid Chamran University of Ahvaz, Ahvaz 61336-3337, Iran.

ABSTRACT
Long non-coding RNAs (lncRNAs) refer to a group of RNAs that are usually more than 200 nucleotides and are not involved in protein generation. Instead, lncRNAs are involved in different regulatory processes, such as regulation of gene expression. Different lncRNAs exist throughout the genome. LncRNAs are also known for their roles in different human diseases such as cancer. HOTAIR is an lncRNA that plays a role as an oncogenic molecule in different cancer cells, such as breast, gastric, colorectal, and cervical cancer cells. Therefore, HOTAIR expression level is a potential biomarker for diagnostic and therapeutic purposes in several cancers. This RNA takes part in epigenetic regulation of genes and plays an important role in different cellular pathways by interacting with Polycomb Repressive Complex 2 (PRC2). In this review, we describe the molecular function and regulation of HOTAIR and its role in different types of cancers.

No MeSH data available.


Related in: MedlinePlus

The RNAs recruiting PRC2 complex inhibit PRC2 function. These RNAs guide PRC2 to its target gene and inhibits EZH2 enzymatic activity at the same time. When PRC2 reaches its target gene, another protein called JARID2 comes into play and binds to EZH2, weakens EZH2-RNA binding, and consequently activates EZH2’s function.
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f1: The RNAs recruiting PRC2 complex inhibit PRC2 function. These RNAs guide PRC2 to its target gene and inhibits EZH2 enzymatic activity at the same time. When PRC2 reaches its target gene, another protein called JARID2 comes into play and binds to EZH2, weakens EZH2-RNA binding, and consequently activates EZH2’s function.

Mentions: HOTAIR is a trans-acting lncRNA and has different target loci such as HOXD4. HOTAIR interacts with Polycomb Repressive Complex 2 (PRC2) and is necessary for PRC2 occupancy and histone H3 lysine-27 trimethylation of different genes in different chromosomes. PRC2 is a histone methyltransferase that implements epigenetic silencing during different processes including cancer development20. HOTAIR localizes and targets PRC2 genome wide21. PRC2 is a complex that contains three major subunits, including EZH2, SUZ12, and EED. Although EZH2 is the key player for the methyltransfer process, other subunits are also required to regulate EZH2 catalytic activity22. The affinity of EZH2 to RNA is regulated by EED, which increases the specificity of PRC2 function. Cifuentes-Rojas et al.23 investigated the PRC2-RNA interaction precisely. They showed that RNA directs PRC2 to its target gene and simultaneously inhibits the enzymatic activity of EZH2. When PRC2 reaches its target gene, JARID2 binds to EZH2 to impair PRC2’s binding to RNA and thereby activates EZH2’s function (Figure 1). Knockdown of JARID2 results in reduction of H3K27me3 levels on some target genes24. JARID2 also may have a negative impact on PRC2’s function, and deletion of JARID2 results in the enhancement of H3K27me3 levels on some target genes25. HOTAIR functions as a molecular scaffold and interacts not only with PRC2 but also with LSD1 complex to regulate gene expression. LSD1 involves in demethylation of histone H3 at lysine 426,27 (Figure 2). Specifically, PRC2 binds to a 5' domain and LSD1 to a 3' domain of HOTAIR, and HOTAIR coordinates their functions for chromatin modification28. Through these functions, HOTAIR affects the expression of multiple genes involved in various cellular functions21.


HOTAIR: an oncogenic long non-coding RNA in different cancers.

Hajjari M, Salavaty A - Cancer Biol Med (2015)

The RNAs recruiting PRC2 complex inhibit PRC2 function. These RNAs guide PRC2 to its target gene and inhibits EZH2 enzymatic activity at the same time. When PRC2 reaches its target gene, another protein called JARID2 comes into play and binds to EZH2, weakens EZH2-RNA binding, and consequently activates EZH2’s function.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4383848&req=5

f1: The RNAs recruiting PRC2 complex inhibit PRC2 function. These RNAs guide PRC2 to its target gene and inhibits EZH2 enzymatic activity at the same time. When PRC2 reaches its target gene, another protein called JARID2 comes into play and binds to EZH2, weakens EZH2-RNA binding, and consequently activates EZH2’s function.
Mentions: HOTAIR is a trans-acting lncRNA and has different target loci such as HOXD4. HOTAIR interacts with Polycomb Repressive Complex 2 (PRC2) and is necessary for PRC2 occupancy and histone H3 lysine-27 trimethylation of different genes in different chromosomes. PRC2 is a histone methyltransferase that implements epigenetic silencing during different processes including cancer development20. HOTAIR localizes and targets PRC2 genome wide21. PRC2 is a complex that contains three major subunits, including EZH2, SUZ12, and EED. Although EZH2 is the key player for the methyltransfer process, other subunits are also required to regulate EZH2 catalytic activity22. The affinity of EZH2 to RNA is regulated by EED, which increases the specificity of PRC2 function. Cifuentes-Rojas et al.23 investigated the PRC2-RNA interaction precisely. They showed that RNA directs PRC2 to its target gene and simultaneously inhibits the enzymatic activity of EZH2. When PRC2 reaches its target gene, JARID2 binds to EZH2 to impair PRC2’s binding to RNA and thereby activates EZH2’s function (Figure 1). Knockdown of JARID2 results in reduction of H3K27me3 levels on some target genes24. JARID2 also may have a negative impact on PRC2’s function, and deletion of JARID2 results in the enhancement of H3K27me3 levels on some target genes25. HOTAIR functions as a molecular scaffold and interacts not only with PRC2 but also with LSD1 complex to regulate gene expression. LSD1 involves in demethylation of histone H3 at lysine 426,27 (Figure 2). Specifically, PRC2 binds to a 5' domain and LSD1 to a 3' domain of HOTAIR, and HOTAIR coordinates their functions for chromatin modification28. Through these functions, HOTAIR affects the expression of multiple genes involved in various cellular functions21.

Bottom Line: Instead, lncRNAs are involved in different regulatory processes, such as regulation of gene expression.Different lncRNAs exist throughout the genome.This RNA takes part in epigenetic regulation of genes and plays an important role in different cellular pathways by interacting with Polycomb Repressive Complex 2 (PRC2).

View Article: PubMed Central - PubMed

Affiliation: Department of Genetics, Faculty of Science, Shahid Chamran University of Ahvaz, Ahvaz 61336-3337, Iran.

ABSTRACT
Long non-coding RNAs (lncRNAs) refer to a group of RNAs that are usually more than 200 nucleotides and are not involved in protein generation. Instead, lncRNAs are involved in different regulatory processes, such as regulation of gene expression. Different lncRNAs exist throughout the genome. LncRNAs are also known for their roles in different human diseases such as cancer. HOTAIR is an lncRNA that plays a role as an oncogenic molecule in different cancer cells, such as breast, gastric, colorectal, and cervical cancer cells. Therefore, HOTAIR expression level is a potential biomarker for diagnostic and therapeutic purposes in several cancers. This RNA takes part in epigenetic regulation of genes and plays an important role in different cellular pathways by interacting with Polycomb Repressive Complex 2 (PRC2). In this review, we describe the molecular function and regulation of HOTAIR and its role in different types of cancers.

No MeSH data available.


Related in: MedlinePlus