Role of LMO7 in cancer (Review)

Abstract

Cancer constitutes a multifaceted ailment characterized by the dysregulation of numerous genes and pathways. Among these, LIM domain only 7 (LMO7) has emerged as a significant player in various cancer types, garnering substantial attention for its involvement in tumorigenesis and cancer progression. This review endeavors to furnish a comprehensive discourse on the functional intricacies and mechanisms of LMO7 in cancer, with a particular emphasis on its potential as both a therapeutic target and prognostic indicator. It delves into the molecular attributes of LMO7, its implications in cancer etiology and the underlying mechanisms propelling its oncogenic properties. Furthermore, it underscores the extant challenges and forthcoming prospects in targeting LMO7 for combating cancer.

Keywords: LIM domain only 7; cancer; tumorigenesis.

Figure 1.

Bioinformatics analysis of H. sapiens LOM7. (A) LMO7 contains LIM domain at its C-terminus, one CH domain at its N-terminus, a PDZ domain in the middle region and two DUF4757 domains of unknown function. (B) Homology tree: The amino acid sequence of H. sapiens LOM7 was compared with known LMO7 proteins of other species. (C) Protein-protein interaction network of LMO7. LMO7 (LIM domain only 7). NECTIN1/2, nectin cell adhesion molecule 1/2; AFDN, afadin; VCL, vinculin; ACTIN1/4, cytoplasmic 1/4; EMD, enamel matrix derivatives; EDNRB, endothelin receptor type B; UCHL1/3, ubiquitin carboxyl-terminal hydrolase isozyme L1/3; COMMD6/9, COMM domain-containing protein 6/9; FBXL15, F-box/LRR-repeat protein 15; FBXW11, F-box and WD-40 domain protein 11; SKP1/2, S-phase kinase associated protein 1/2; CDK2, cyclin-dependent kinase 2; FBXO4, F-box protein 4; NFKBIA, nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha; RBX1, ring box protein 1.

Figure 2.

Gene expression profile across all T and N samples. Each dot represents the expression in a sample. The red font indicates that the TPM of LMO7 is significantly upregulated in this tumor type, the green font indicates that the TPM of LMO7 is significantly downregulated in this tumor type and the black font indicates that there is no significant difference between T and N samples. The data were obtained from GEPIA 2. LMO7, LIM domain only 7; T, tumor; N, paired normal tissues; ACC, adrenocortical carcinoma; BLCA, bladder urothelial carcinoma; BRCA, breast invasive carcinoma; CESC, cervical squamous cell carcinoma and endocervical adenocarcinoma; CHOL, cholangiocarcinoma; COAD, colon adenocarcinoma; DLBC, lymphoid neoplasm diffuse large B-cell lymphoma; ESCA, esophageal cancer; GBM, glioblastoma multiforme; HNSC, head and neck squamous cell carcinoma; KICH, kidney chromophobe; KIRC, kidney renal clear cell carcinoma; KIRP, kidney renal papillary cell carcinoma; LAML, acute myeloid leukemia; LGG, brain lower grade glioma; LIHC, liver hepatocellular carcinoma; LUAD, lung adenocarcinoma; LUSC, lung squamous cell carcinoma; MESO, mesothelioma; OV, ovarian serous cystadenocarcinoma; PAAD, pancreatic adenocarcinoma; PCPG, pheochromocytoma and paraganglioma; PRAD, prostate adenocarcinoma; READ, rectum adenocarcinoma; SARC, sarcoma; SKCM, skin cutaneous melanoma; STAD, stomach adenocarcinoma; TGCT, testicular germ cell tumors; THCA, thyroid carcinoma; THYM, thymoma; UCEC, uterine corpus endometrial carcinoma; UCS, uterine carcinosarcoma; UVM, uveal melanoma.

Figure 3.

Molecular pathways regulated by LMO7 in tumorigenesis. LMO7 mediates signal transduction pathways and controls the expression of target genes by interacting with different proteins. LMO7 interacts with AKT to enhance the activity of the PI3K/AKT/mTOR pathway and Rho-GTPase. LMO7 interacts with c-Fos and c-Jun, promoting their degradation and interrupting activator protein 1-dependent TGF-β autoinduction. LMO7 and TGF-β form a negative feedback loop to regulate cell proliferation, invasion and migration, leading to tumorigenesis. LMO7, LIM domain only 7; EMT, epithelial to mesenchymal transition; PI3K, phosphoinositide3-kinase; AKT, serine/threonine-protein kinase; mTOR, mechanistic target of rapamycin; Rho-GTPase, rhodopsin-guanosine triphosphatase; MEK1/2, MAP kinase kinase 1/2; MAPK, mitogen-activated protein kinase; c-Fos, Fos proto-oncogene; c-Jun, Jun proto-oncogene; Snail, snail family transcriptional repressor 1; ZEB1, zinc finger E-box binding homeobox 1; Slug, snail family transcriptional repressor 2; CTCF, CCCTC-binding factor; Smad3, SMAD family member 3; TGF-β, transforming growth factor β; TβR-I/II, transforming growth factor beta receptor I/II; integrin-αvβ3, integrin subunit αVβ3; AP-1, activator protein 1.

Figure 4.

Overall survival analysis based on LMO7 expression. Correlation between high LMO7 TPM and decreased overall survival in BRCA, ACC, BLCA, HNSC, LGG, LUSC, PAAD, PCPG, GBM, UCEC, OV and UVM. Correlation between low LMO7 (TPM) and decreased overall survival in COAD, CESC and CHOL. Data were obtained from GEPIA 2. LMO7, LIM domain only 7; TPM, transcripts per million; HR, hazard ratio; BRCA, breast invasive carcinoma; ACC, adrenocortical carcinoma; BLCA, bladder urothelial carcinoma; HNSC, head and neck squamous cell carcinoma; LGG, brain lower grade glioma; LUSC, lung squamous cell carcinoma; PAAD, pancreatic adenocarcinoma; PCPG, pheochromocytoma and paraganglioma; GBM, glioblastoma multiforme; UCEC, uterine corpus endometrial carcinoma; OV, ovarian serous cystadenocarcinoma; UVM, uveal melanoma; COAD, colon adenocarcinoma; CESC, cervical squamous cell carcinoma and endocervical adenocarcinoma; CHOL, cholangiocarcinoma.

Figure 5.

The genomic alterations of LMO7 in different tumors were divided into four categories: Mutation, amplification, deep deletion and structural variant. Among them, mutation and amplification were the most frequent alterations. Data were obtained from the cBioPortal for Cancer Genomics.