LMO1 (LIM Domain Only 1), also known as Rhombotin-1, is a nuclear transcriptional cofactor encoded by the LMO1 gene located on human chromosome 11 (11p15.4). It belongs to the LIM-only protein family, characterized by two zinc-finger LIM domains that mediate protein-protein interactions . LMO1 functions as a scaffold in transcriptional complexes, regulating gene expression in developmental and pathological contexts. Its dysregulation is implicated in various cancers, including glioma, neuroblastoma, gastric cancer, and lung cancer .
LMO1 lacks intrinsic transcriptional activation/repression domains but interacts with transcription factors (e.g., GATA3, TAL1) to modulate gene expression . Key structural and functional features include:
Zinc-finger LIM domains: Critical for binding partners like GATA proteins .
Tissue-specific expression: Elevated in neural crest-derived cells and tumors .
Regulatory polymorphisms: Genetic variants (e.g., rs2168101) influence cancer susceptibility by altering transcription factor binding .
LMO1 exhibits oncogenic roles in multiple cancers, with distinct mechanisms:
| Cohort | Molecular Subgroup | LMO1 Expression | Survival Outcome | Source |
|---|---|---|---|---|
| TCGA | IDH-wt | High | Reduced OS (HR >1.5) | |
| CGGA | 1p/19q non-codeletion | High | Poor prognosis | |
| GSE16011 | Glioma patients | High | Shorter OS |
Genetic predisposition:
Mechanisms:
What is the role of LMO1 in human glioma progression?
How can LMO1 expression be used as a prognostic biomarker for glioma?
What experimental techniques are commonly used to study LMO1 in gliomas?
What is the relationship between LMO1 and NGFR in gliomas?
How does the molecular context (e.g., IDH status or 1p/19q co-deletion) affect the prognostic value of LMO1?
What experimental designs can be used to validate LMO1 as a therapeutic target?
To validate LMO1 as a therapeutic target, researchers can design knockout models using CRISPR/Cas9 or RNA interference (siRNA). Functional assays measuring proliferation, migration, and invasion in glioma cells can confirm its role. Additionally, in vivo studies with nude mice can test tumor growth inhibition upon LMO1 silencing .
How does chemoresistance and radioresistance correlate with LMO1 expression?
What are the challenges in translating findings on LMO1 to clinical applications?
How can data contradictions regarding LMO1's role be resolved?
What are the ethical considerations when studying human glioma tissues for LMO1 research?
How can bioinformatics tools enhance research on LMO1?
What statistical models are suitable for analyzing survival data related to LMO1 expression?
LIM Domain Only 1 (LMO1) is a member of the LIM-only (LMO) family of genes, which encode transcriptional cofactors. These cofactors play a crucial role in regulating gene transcription by acting as key connectors or scaffolds in transcription complexes . The LMO family consists of four members: LMO1, LMO2, LMO3, and LMO4 .
The LMO1 gene is located on human chromosome 11p15.4 and is also known as T-cell translocation gene 1 (TTG-1) or rhombotin . The LMO1 protein is characterized by the presence of LIM domains, which are specialized zinc-binding domains that mediate protein-protein interactions . The human recombinant LMO1 protein is typically produced in Escherichia coli (E. coli) and consists of 179 amino acids, with a molecular mass of approximately 20.2 kDa .
LMO1 functions as a transcriptional cofactor, meaning it does not directly bind to DNA but instead interacts with other transcription factors to regulate gene expression . This protein is involved in various biological processes, including cell differentiation, development, and tumorigenesis . LMO1 has been shown to play a critical oncogenic role in several types of cancers, such as T-cell acute lymphoblastic leukemia, neuroblastoma, gastric cancer, lung cancer, and prostate cancer .
The oncogenic activity of LMO1 is primarily attributed to its ability to form transcriptional complexes with other proteins, thereby influencing the expression of genes involved in cell proliferation and survival . The molecular mechanisms underlying LMO1’s functions are complex and not fully understood, but they involve interactions with various transcription factors and co-regulators .
Given its role in tumorigenesis, LMO1 is a potential target for cancer diagnosis and therapy . Understanding the mechanisms that drive its aberrant activation in cancers could lead to the development of novel therapeutic strategies. Additionally, LMO1’s involvement in non-cancer diseases and developmental processes highlights its broader significance in human biology .