Neuritin 1 expression in human normal tissues and its association with various human cancers

Neuritin (Nrn1) is a glycophosphatidylinositol-linked protein that can be induced by neural activity in the central nervous system. However, its expression outside the nervous system and association with human cancers is unclear. This study investigated the expression of Nrn1 in human tissues as well as its association with human cancers.

Nrn1 gene expression in human adult tissues was evaluated with the Clontech Multiple Tissue cDNA panel. Nrn1 protein in various tissues was detected by immunohistochemistry. Signal v.4.0 and TMHMM v.2.0 software were used to identify the signal peptide and transmembrane helix of Nrn1. The subcellular localization of Nrn1 in cultured SH-SY5Y cells was assessed by immunocytochemistry and western blotting. The expression of Nrn1 in human cancers were assessed using the online tools GEPIA.

Nrn1 mRNA was expressed in various tissues, compared to mRNA levels in the brain tissues, expression was high in the placenta, lungs, skeletal muscle, thymus, pancreas, liver and the heart tissues; lower levels were detected in the small intestine, ovary, spleen, and testes, but there was no detectable expression in the kidneys, colon, prostate or leukocytes. In SY5Y cells, Nrn1 was colocalized with caveolin 1 at the plasma membrane. Nrn1 was downregulated in Bladder Urothelial Carcinoma (BLCA); Breast invasive carcinoma (BRCA); Cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC); Colon adenocarcinoma (COAD); Glioblastoma multiforme (GBM); Kidney Chromophobe (KIHC); Kidney renal papillary cell carcinoma (KIRP); Lower Grade GLioma (LGG); Rectum adenocarcinoma (READ); Uterine Corpus Endometrial Carcinoma (UCEC); Lung adenocarcinoma (LUA), Ovarian serous cystadenocarcinoma (OV) and upregulated in Lymphoid Neoplasm Diffuse Large B-cell Lymphoma (DLBC). A combination of the overall survival analysis of the 12 kinds of human tumors with Nrn1 downregulation revealed that patients with high levels of Nrn1 present a long term survival. But there is no significant effect on DLBC patients' survival.

Nrn1 is expressed in various human tissues including the nervous system, specifically in the lipid rafts of cell membranes. We also provided the strong evidence that Nrn1 is associated with 13 kinds of human cancers and could function as biomarkers and therapeutic targets for these cancers.