Serpine2

Fig1. Role of PN-1 in hemostasis and vascular biology. (Marie-Christine Bouton, 2012)

What is SERPINE2 protein?

SERPINE2 (serpin family E member 2) gene is a protein coding gene which situated on the long arm of chromosome 2 at locus 2q36. SERPINE2 protein is also known as PN1. It belongs to the serpin superfamily, a group of proteins known for their ability to inhibit serine proteases, enzymes that play a key role in many biological processes including blood clotting, digestion, and the immune response. As a serpin, SERPINE2 has a conserved structural motif that allows it to function as an inhibitory protein, although the exact mechanisms of its action are still under investigation. The SERPINE2 protein is consisted of 398 amino acids and its molecular mass is approximately 44.0 kDa.

What is the function of SERPINE2 protein?

Like other serpins, SERPINE2 is capable of inhibiting serine proteases, although its specific target proteases and physiological role in this regard are not as well established as some other serpins. SERPINE2 has been implicated in cell migration and adhesion processes, which are important for tissue repair, immune response, and tumor metastasis. It has been suggested that SERPINE2 may play a role in angiogenesis, the formation of new blood vessels, which is a critical process in development, wound healing, and tumor growth. SERPINE2 is expressed in various tissues and has been associated with tissue repair and regeneration, particularly in the context of liver and testicular tissue. SERPINE2 has been found to interact with other proteins and may be involved in gene regulation processes.

SERPINE2 Related Signaling Pathway

SERPINE2 is involved in pathways that regulate cell migration and adhesion, which are crucial for processes like tissue repair, immune cell trafficking, and tumor metastasis. It has been suggested that SERPINE2 may be involved in angiogenesis, the formation of new blood vessels, which is regulated by various signaling pathways including those involving VEGF (Vascular Endothelial Growth Factor) and FGF (Fibroblast Growth Factor). As SERPINE2 is expressed during embryonic development, it may be part of signaling pathways that regulate organogenesis and morphogenesis. It is possible that SERPINE2 interacts with signaling pathways that regulate apoptosis or programmed cell death, which is a critical process in development, immune function, and disease.

SERPINE2 Related Diseases

SERPINE2 has been associated with various types of cancer. It may play a role in tumor progression, metastasis, and angiogenesis, and is being explored as a potential therapeutic target for cancer treatment. SERPINE2's role in maintaining the integrity of the Blood-Brain Barrier (BBB) Disorders makes it a potential factor in diseases where the barrier's integrity is compromised, such as multiple sclerosis. Alterations in SERPINE2 have been linked to Cerebral Cavernous Malformations (CCM), which are abnormally dilated capillaries in the brain and spinal cord that can lead to bleeding and neurological symptoms.

Bioapplications of SERPINE2

Because SERPINE2 has an anticoagulant effect, it has the potential to be developed into a new type of anticoagulant for the prevention and treatment of thrombotic diseases. In the field of biotechnology, SERPINE2 can be used to produce bioactive substances such as anticoagulases and antiplatelet aggregators. SERPINE2 can also be used in the food industry, such as making anti-clotting foods to prevent cardiovascular disease.

Case Study 1: Boxuan Zhou, 2023

Circular RNAs (circRNAs) have important regulatory functions in cancer, but the role of circRNAs in the tumor microenvironment (TME) remains unclear. Moreover, the researchers also explore the effects of si-circRNAs loaded in nanoparticles as therapeutic agent for anti-tumor in vivo. They conducted bioinformatics analysis, qRT-PCR, EdU assays, Transwell assays, co-culture system and multiple orthotopic xenograft models to investigate the expression and function of circRNAs. They identified oncogene SERPINE2 derived circRNA, named as cSERPINE2, which was notably elevated in breast cancer and was closely related to poor clinical outcome. Functionally, tumor exosomal cSERPINE2 was shuttled to tumor associated macrophages (TAMs) and enhanced the secretion of Interleukin-6 (IL-6), leading to increased proliferation and invasion of breast cancer cells. More importantly, they developed a PLGA-based nanoparticle loaded with si-cSERPINE2, which effectively attenuated breast cancer progression in vivo.

Fig1. cSERPINE2 silenced EO771 cells were used to constructed orthotopic tumor models. Tumor size was measured over time.

Fig2. Orthotopic breast cancer models were injected exosomes derived from EO771 cells with or without cSERPINE2 overexpression.

Case Study 2: Guoyou Zou, 2022

Serpin family E member 2 (SERPINE2) is overexpressed in a variety of tumors, especially adenocarcinoma, and promotes tumor invasion and metastasis. The function and mechanism of SERPINE2 in HB are still unclear. The purpose of this study was to investigate the potential clinical prognostic value and molecular mechanism of SERPINE2 in Hepatoblastoma (HB). The expression level of SERPINE2 in HB and its clinical significance were further analyzed by quantitative real-time polymerase chain reaction (qRT-PCR), Western blot, and immunohistochemistry. After constructing the SERPINE2 overexpression and knockdown in HepG2 and HUH6 cells, the 5-ethynyl-29-deoxyuridine (EdU) assay, wound healing assay, Transwell experiment, and apoptosis assay were performed to explore the role of SERPINE2 in HB progress. The results showed that the SERPINE2 expression was related to tumor size, vascular invasion, and tumor metastasis. The Cox regressions show that high SERPINE2 expression is an independent risk factor for HB. SERPINE2 overexpression remarkably enhanced HB cell migration and invasion and suppressed apoptosis, while knockdown of SERPINE2 exerted the opposite effect. In addition, SERPINE2 facilitated the epithelial to mesenchymal transformation (EMT) phenotype of HB cells in vitro.

Fig3. The expression of SERPINE2 in hepatoblastoma and normal liver.

Fig4. Western blot analysis of E-cadherin and N-cadherin in HepG2 cells transfected with OE-SERPINE2 group and si-SERPINE2 group.

Serpine2 has several biochemical functions, for example, glycosaminoglycan binding,heparin binding,protein binding. Some of the functions are cooperated with other proteins, some of the functions could acted by Serpine2 itself. We selected most functions Serpine2 had, and list some proteins which have the same functions with Serpine2. You can find most of the proteins on our site.

Serpine2 has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with Serpine2 here. Most of them are supplied by our site. Hope this information will be useful for your research of Serpine2.

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