NET1

Official Full Name

neuroepithelial cell transforming 1

Organism

Homo sapiens

GeneID

10276

Background

This gene is part of the family of Rho guanine nucleotide exchange factors. Members of this family activate Rho proteins by catalyzing the exchange of GDP for GTP. The protein encoded by this gene interacts with RhoA within the cell nucleus and may play a role in repairing DNA damage after ionizing radiation. Pseudogenes of this gene are located on the long arms of chromosomes 1, 7 and 18. Alternative splicing results in multiple transcript variants that encode different protein isoforms. [provided by RefSeq, Jul 2012]

Synonyms

NET1A; ARHGEF8;

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Detailed Information

The NET-1 gene is a member of the newly discovered protein superfamily, especially in tumor tissues. The study found that NET-1 is closely related to tumor cell proliferation, adhesion, migration, invasion and induction of vascular formation, and has certain value for prognosis. The NET-1 gene and NET-2, NET-3, NET-4, NET-5, NET-6, and NET-7 are collectively referred to as NET-X and belong to one of the members of the tetrameric superfamily (TM4SF).

NET1 Features

Collectively known as net-x, net-1 and net-2 ~ 7 are members of seven new transmembrane 4 superfamily or tetraspan family (TM4SF) identified in the EST database in 2000 by Serru. Studies have shown that TM4SF acts as a molecular service protein to enhance functional signaling by linking specific cell surface proteins (such as lineage-specific proteins, integrins, other TM4SF molecules, etc.), which can transduce the formation and stability of complexes. Through this process, TM4SF is involved in cell activation and proliferation, adhesion and migration, differentiation and carcinogenesis.

Figure 1. An integrated model for the activation of canonical Wnt signaling by Net1. (Wei, S., et al. 2016)

Studies have shown that NET-1 mRNA is expressed in tumors such as cervical cancer, liver cancer, rectal cancer, gastric cancer and pancreatic cancer. At present, NET-1 is rarely reported in domestic and foreign literatures in lung cancer, esophageal cancer, and ovarian cancer. The study used RT-PCR to detect NET-1 and NET-7 genes in a variety of human cell lines. In addition, RT-PCR was used to screen 48 tissues and corresponding tumors in humans. It was found that NET-1 was expressed in almost all human tissues and corresponding tumors except for hematopoietic tissues and corresponding tumors, as well as the heart, brain and pancreas.

NET-1 and Tumor

RT-PCR was used to detect the expression of NET-1 gene in cervical cancer by mRNA level and immunohistochemical staining. The results showed that the NET-1 gene was expressed in CINIII and cervical squamous cell carcinoma, adenocarcinoma and cervical undifferentiated carcinoma. To investigate the expression of cyclooxygenase-2 (COX-2) and NET-1 gene in cervical cancer, it was found that NET-1 is not expressed in normal cervical tissues and is hardly expressed in CINI, but in CINII and CINIII. NET-1 positive cells gradually increase and spread throughout the epithelial layer. Similar to the reports of Wollscheid et al, the positive expression rates of NET-1 in CINIII and cervical cancer were 78.6% and 76.0%, respectively. The positive expression rate of CINIII was significantly higher than that of CINI and CINII, but before cervical cancer infiltration. There were no significant differences in the stages of cancer development. It suggests that the overexpression of NET-1 may be an early molecular event of cervical cancer, and NET-1 may be a tissue marker for early diagnosis of cervical cancer.

NET-1 protein is positively expressed in cytoplasm or membrane in hepatocellular carcinoma, and the positive rate is higher than that in adjacent tissues, suggesting that NET-1 as a membrane protein and cytoplasmic protein may transduce cell division signals and/or cause cell differentiation or dedifferentiation. Therefore, the function of liver cancer cells may be related to the accumulation of surface protein NET-1 in cancer cell populations. These proteins may synergistically produce tumor cell growth factors and promote tumor proliferation, suggesting that NET-1 gene may promote tumor formation, which may be a new marker in learning liver cancer tissue. 28 cases of paracancerous and non-cancerous liver tissue hepatocytes were pathologically characterized by varying degrees of hyperplasia, dysplasia or adenomatous hyperplasia, accompanied by cirrhosis or hepatitis background. Paracancerous cells may be transformed cells between normal cells and cancer cells, and NET-1 expression appears in this cell, suggesting that NET-1 expression may be an early event in liver cancer.

References:

Wei, S. , Dai, M. , Liu, Z. , Ma, Y. , Shang, H. , & Cao, Y. , et al. (2016). The guanine nucleotide exchange factor net1 facilitates the specification of dorsal cell fates in zebrafish embryos by promoting maternal β-catenin activation. Cell Research.
Sun, X. , Wang, M. , Zhang, F. , & Kong, X. . (2019). Inhibition of net 1 suppresses proliferation and promotes apoptosis of hepatocellular carcinoma cells by activating the pi3k/akt signaling pathway. Experimental and Therapeutic Medicine.
Xitian, L. , Bolin, W. , Haitao, S. , Xue, H. , Hui, J. , & Yixin, S. , et al. (2018). Vtiq evaluates antitumor effects of net?1 sirna by utmd in hcc xenograft models. Oncology Letters.

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