LRIG3 (Leucine-Rich Repeats And Immunoglobulin-Like Domains 3)
2014-05-01 Dongsheng Guo , Feng Mao , Ting Lei AffiliationDept of Neurosurgery,Tongji Hospital, Huazhong University of Sciences, Technology, Wuhan, Hubei, 430030, Peoples Republic of China
Abstract
LRIG3 is a member of mammalian LRIG family and less is known about the functions of LRIG3. Accumulating evidences showed that LRIG3 may also function as a tumor suppressor like LRIG1. LRIG3 can inhibit tumor cell proliferation, survival, adhesion and invasion in many types of human cancer cells based on cell experiments. Perinuclear staining of LRIG3 correlated with better survival in astrocytic tumors. Decreased LRIG3 was identified as one of 12 promising serum biomarkers for early stage non-small-cell lung cancer. LRIG3 may play a role in inner ear morphogenesis and neural crest formation.
DNA/RNA
Description
According to Entrez-Gene, LRIG3 gene maps to NC_000012.12 in the region between 58872155 and 58920538 and spans across 48.3 kilobases. LRIG3 gene is encoded on the reverse strand.
Transcription
Homo sapiens leucine-rich repeats and immunoglobulin-like domains 3 has at least two transcript variants. The pre-mRNAs comprise 19 exons. The coding sequence of transcript variant 1 (NM_001136051.2) and 2 (NM_153377.4) is 3691bp and 4110bp respectively.
Proteins
LRIG3 protein. SP: signal peptide; NF: N-terminal cysteine-rich flanking domain; LRRs: 15 leucine-rich repeats; CF: C-terminal cysteinerich flanking domain; Ig C2: C2-type immunoglobulin-like domains; TM: transmembrane domain; Cyto: cytoplasmic domain.
Description
LRIG3 is a transmembrane cell-surface protein consisting of 1059 or 1119 amino acids. LRIG3 contains a signal peptide, 15 tandem LRR with cysteine rich N- and C-flanking domains, three immunoglobulin-like domains, a transmembrane domain, and a cytoplasmic tail.
Expression
LRIG3 is ubiquitously expressed in human organs. The highest expression of LRIG3 is in stomach, thyroid, and skin.
Localisation
Differential subcellular expression in a cell type-sepcific manner.
Function
LRIG3 may function as a tumor suppressor.
Mutations
Note
Mutations in LRIG3 are rare, according to the TCGA data set.
Implicated in
Entity name
Ependymoma
Note
Perinuclear staining of LRIG3 was significantly lower in posterior fossa ependymomas than in supratentorial ependymomas (Yi et al., 2009).
Entity name
Pituitary adenoma
Note
The expression of LRIG 3 in HP75 cell line was lower compared to normal pituitary glands (Guo et al., 2007).
Entity name
Astrocytic tumors
Note
Perinuclear expression of LRIG3 in astrocytic tumors has been associated with better patient survival (Guo et al., 2006). Down-regulation of LRIG3 expression in glioblastoma cell lines resulted in increased proliferation and invasion, decreased apoptosis, and increased EGFR expression (Cai et al., 2009).
Entity name
Cervical adenocarcinoma
Note
High fraction of LRIG3-positive cells were significantly associated with patient survival, and LRIG3 staining intensity was positively correlated with HPV status (Muller et al., 2013).
Entity name
Non-small-cell lung cancer
Note
LRIG3 downregulation was identified as one of 12 promising serum biomarkers for early stage non-small-cell lung cancer (Ostroff et al., 2010).
Fusion protein
The LRIG3-ROS1 fusion has been identified in non-small-cell lung cancer (Cai et al., 2013).
Entity name
Psoriasis
Note
The expression pattern of LRIG3 protein was altered in psoriatic lesions compared to normal skin (Karlsson et al., 2008).
Entity name
Inner ear morphogenesis
Note
During inner ear development, Lrig3 acts to repress Netrin transcription and Lrig3 loss led to defects in inner ear morphogenesis (Abraira et al., 2008).
Entity name
Neural crest formation
Note
LRIG3 is required for neural crest formation in developing Xenopus embryos by regulating the Wnt and Fgf signaling pathways (Zhao et al., 2008).
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 20126551 | 2010 | Vertebrate Lrig3-ErbB interactions occur in vitro but are unlikely to play a role in Lrig3-dependent inner ear morphogenesis. | Abraira VE et al |
| 19200647 | 2009 | Inhibition of LRIG3 gene expression via RNA interference modulates the proliferation, cell cycle, cell apoptosis, adhesion and invasion of glioblastoma cell (GL15). | Cai M et al |
| 19224171 | 2009 | Effects of RNAi-mediated gene silencing of LRIG3 expression on cell cycle and survival of glioma cells. | Cai M et al |
| 23514723 | 2013 | ROS1 fusions in Chinese patients with non-small-cell lung cancer. | Cai W et al |
| 24086156 | 2013 | In vivo analysis of Lrig genes reveals redundant and independent functions in the inner ear. | Del Rio T et al |
| 22484910 | 2012 | Immunohistochemical analysis of LRIG proteins in meningiomas: correlation between estrogen receptor status and LRIG expression. | Ghasimi S et al |
| 17393120 | 2007 | Down-regulation of leucine-rich repeats and immunoglobulin-like domain proteins (LRIG1-3) in HP75 pituitary adenoma cell line. | Guo D et al |
| 15203213 | 2004 | The LRIG gene family has three vertebrate paralogs widely expressed in human and mouse tissues and a homolog in Ascidiacea. | Guo D et al |
| 16532360 | 2006 | Perinuclear leucine-rich repeats and immunoglobulin-like domain proteins (LRIG1-3) as prognostic indicators in astrocytic tumors. | Guo D et al |
| 18037903 | 2008 | Redistribution of LRIG proteins in psoriasis. | Karlsson T et al |
| 23165628 | 2013 | Expression of LRIG1 and LRIG3 correlates with human papillomavirus status and patient survival in cervical adenocarcinoma. | Muller S et al |
| 21170350 | 2010 | Unlocking biomarker discovery: large scale application of aptamer proteomic technology for early detection of lung cancer. | Ostroff RM et al |
| 23392718 | 2013 | Over-expression of LRIG3 suppresses growth and invasion of bladder cancer cells. | Qi Y et al |
| 23723069 | 2013 | Leucine-rich repeat and immunoglobulin domain-containing protein-1 (Lrig1) negative regulatory action toward ErbB receptor tyrosine kinases is opposed by leucine-rich repeat and immunoglobulin domain-containing protein 3 (Lrig3). | Rafidi H et al |
| 22893457 | 2012 | Activin and BMP4 synergistically promote formation of definitive endoderm in human embryonic stem cells. | Teo AK et al |
| 23558895 | 2013 | LRIG1 is a triple threat: ERBB negative regulator, intestinal stem cell marker and tumour suppressor. | Wang Y et al |
| 21417672 | 2012 | Expression of EGFR and LRIG proteins in oesophageal carcinoma with emphasis on patient survival and cellular chemosensitivity. | Wu X et al |
| 22038358 | 2011 | Effect of over-expressed LRIG3 on cell cycle and survival of glioma cells. | Yang H et al |
| 19216216 | 2009 | Expression of leucine-rich repeats and immunoglobulin-like domains (LRIG) proteins in human ependymoma relates to tumor location, WHO grade, and patient age. | Yi W et al |
| 21505989 | 2011 | Effect of silencing LRIG3 gene on the proliferation and apoptosis of bladder cancer T24 cells. | Yuan X et al |
| 18287203 | 2008 | Lrig3 regulates neural crest formation in Xenopus by modulating Fgf and Wnt signaling pathways. | Zhao H et al |
Other Information
Locus ID:
NCBI: 121227
MIM: 608870
HGNC: 30991
Ensembl: ENSG00000139263
Variants:
dbSNP: 121227
ClinVar: 121227
TCGA: ENSG00000139263
COSMIC: LRIG3
RNA/Proteins
Expression (GTEx)
Protein levels (Protein atlas)
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 36639372 | 2023 | Glioma-derived LRIG3 interacts with NETO2 in tumor-associated macrophages to modulate microenvironment and suppress tumor growth. | 3 |
| 36639372 | 2023 | Glioma-derived LRIG3 interacts with NETO2 in tumor-associated macrophages to modulate microenvironment and suppress tumor growth. | 3 |
| 34839782 | 2022 | Prognostic significance of LRIG2 and LRIG3 proteins in urothelial bladder carcinoma. | 0 |
| 34839782 | 2022 | Prognostic significance of LRIG2 and LRIG3 proteins in urothelial bladder carcinoma. | 0 |
| 33469151 | 2021 | LRIG proteins regulate lipid metabolism via BMP signaling and affect the risk of type 2 diabetes. | 9 |
| 33469151 | 2021 | LRIG proteins regulate lipid metabolism via BMP signaling and affect the risk of type 2 diabetes. | 9 |
| 32107843 | 2020 | LRIG3 represses cell motility by inhibiting slug via inactivating ERK signaling in human colorectal cancer. | 3 |
| 33222697 | 2020 | A novel circular RNA circ-LRIG3 facilitates the malignant progression of hepatocellular carcinoma by modulating the EZH2/STAT3 signaling. | 32 |
| 33287939 | 2020 | miR-196a targeting LRIG3 promotes the proliferation and migration of cervical cancer cells. | 1 |
| 32107843 | 2020 | LRIG3 represses cell motility by inhibiting slug via inactivating ERK signaling in human colorectal cancer. | 3 |
| 33222697 | 2020 | A novel circular RNA circ-LRIG3 facilitates the malignant progression of hepatocellular carcinoma by modulating the EZH2/STAT3 signaling. | 32 |
| 33287939 | 2020 | miR-196a targeting LRIG3 promotes the proliferation and migration of cervical cancer cells. | 1 |
| 30412760 | 2019 | Overexpressed LRIG3 gene ameliorates prostate cancer through suppression of cell invasion and migration. | 4 |
| 30412760 | 2019 | Overexpressed LRIG3 gene ameliorates prostate cancer through suppression of cell invasion and migration. | 4 |
| 27628597 | 2017 | LRIGs: A Prognostically Significant Family with Emerging Therapeutic Competence against Cancers. | 5 |
Citation
Dongsheng Guo ; Feng Mao ; Ting Lei
LRIG3 (Leucine-Rich Repeats And Immunoglobulin-Like Domains 3)
Atlas Genet Cytogenet Oncol Haematol. 2014-05-01
Online version: http://atlasgeneticsoncology.org/gene/47529/new-content/submit-meetings/
