LBX2
| LBX2 | |||||||||||||||||||||||||||||||||||||||||||||||||||
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| Aliases | LBX2, LP3727, ladybird homeobox 2 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | OMIM: 607164; MGI: 1342288; HomoloGene: 36314; GeneCards: LBX2; OMA:LBX2 - orthologs | ||||||||||||||||||||||||||||||||||||||||||||||||||
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Ladybird homeobox 2 (LBX2) is a protein that is encoded by the LBX2 gene, located on the second chromosome[5] in humans, and on the sixth chromosome in mice.[6]
LBX2 belongs to the homeobox gene family, which plays important roles in embryonic development and tissue differentiation. The protein encoded by LBX2 functions as a transcription factor and is expressed in various tissues, including the heart, skeletal muscle, and nervous system. LBX2 is involved in the regulation of cardiac development, particularly in the formation of the atrial septum. Mutations or dysregulation of LBX2 have been associated with an increased risk of congenital heart defects, specifically atrial septal defects.[7]
LBX2 plays a significant role in the development of various organs, such as the heart, and has been implicated in the growth of certain cancers.[8]
Gene structure
[edit]The LBX2 gene shares similarities with its rodent counterpart, also named LBX2, in genomic structure. Both human and rodent LBX2 genes are composed of two exons separated by an intron.[5][9]
The upstream region of the mouse LBX2, which shares a high degree of similarity to its human counterpart, has also been observed to be a regulatory sequence that influences the expression of reporter genes.[10] This regulatory influence is tissue-specific, highlighting the complexity of gene expression in different biological contexts.
Expression and function
[edit]LBX2 is a member of the ladybird family of homeobox genes, which are crucial in developmental processes. In rodent studies, LBX2 has been found to be expressed in various developing systems, notably the urogenital system, eye, and brain.[10]
CRISPR/Cas9 technology has been used to create zebrafish models lacking LBX2. Observations of these modified zebrafish revealed several notable differences compared to normal specimens, including:
- Enlarged heart chambers (the atrium and ventricle)
- Disorganized distribution of cardiac myocytes
- Delayed migration of cardiac neural crest cells[7]
These findings suggest that LBX2 plays a significant role in the development of the heart.
Clinical significance
[edit]Alström syndrome
[edit]While polymorphisms in the LBX2 gene have been identified, studies indicate that mutations in the coding region of LBX2 do not account for Alström syndrome, a genetic disorder characterized by ocular and urogenital abnormalities.[10]
Atrial septal defect
[edit]A study aimed at identifying causal genes for ostium secundum atrial septal defect (ASD) discovered that a rare missense mutation in LBX2 was associated with this condition.[7]
Ovarian cancer
[edit]Laboratory studies have indicated that LBX2 promotes rapid cell proliferation in ovarian cancers and is a key gene involved in ovarian cancer formation. It has been identified as a potential target for therapeutic interventions.[11]
Lung cancer
[edit]Lung adenocarcinoma (LUAD) is the most common type of lung cancer. Studies have shown that reducing LBX2 expression inhibits LUAD growth, whereas its overexpression promotes tumor growth and invasiveness.[12] In most LUAD cases, LBX2 is expressed at elevated levels, correlating with poor clinical outcomes.[12]
Conclusion
[edit]LBX2 is a crucial gene involved in development and disease processes. Its role in the development of organs, particularly in the cardiac and reproductive systems, alongside its implications in cancer biology, emphasise its importance to the healthy development of humans, rodents and zebrafish.
References
[edit]- ^ a b c GRCh38: Ensembl release 89: ENSG00000179528 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000034968 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ a b "LBX2 ladybird homeobox 2 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2024-10-13.
- ^ "Gene: Lbx2 (ENSMUSG00000034968) - Summary - Mus_musculus - Ensembl genome browser 111". jan2024.archive.ensembl.org. Retrieved 2024-10-13.
- ^ a b c Wang J, Luo J, Chen Q, Wang X, He J, Zhang W, et al. (August 2018). "Identification of LBX2 as a novel causal gene of atrial septal defect". International Journal of Cardiology. 265: 188–194. doi:10.1016/j.ijcard.2018.04.038. PMID 29669692.
- ^ Su Y, Li C, Fang Y, Gu X, Zheng Q, Lu J, et al. (February 2023). "The role of LncRNA LBX2-AS1 in cancers: functions, mechanisms and potential clinical utility". Clinical & Translational Oncology. 25 (2): 293–305. doi:10.1007/s12094-022-02944-2. PMC 9873731. PMID 36131071.
- ^ "Lbx2 ladybird homeobox 2 [Rattus norvegicus (Norway rat)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2024-10-13.
- ^ a b c Chen F, Collin GB, Liu KC, Beier DR, Eccles M, Nishina PM, et al. (June 2001). "Characterization of the murine Lbx2 promoter, identification of the human homologue, and evaluation as a candidate for Alström syndrome". Genomics. 74 (2): 219–227. doi:10.1006/geno.2001.6539. PMID 11386758.
- ^ Xiong J, Liang H, Sun X, Gao K (April 2024). "Histone modification-linked prognostic model for ovarian cancer reveals LBX2 as a novel growth promoter". Journal of Cellular and Molecular Medicine. 28 (8): e18260. doi:10.1111/jcmm.18260. PMC 10960176. PMID 38520216.
- ^ a b Hu J, Bai Y, Zhang Q, Li M, Yin R, Xu L (August 2020). "Identification of LBX2 as a novel causal gene of lung adenocarcinoma". Thoracic Cancer. 11 (8): 2137–2145. doi:10.1111/1759-7714.13506. PMC 7396393. PMID 32567804.