Insulin-Like Growth Factor 2 mRNA-Binding Protein 2 (IGFBP2) belongs to the RRM IMP/VICKZ family. IGFBP2 is a cytoplasmic protein and contains four KH domains and two RRM (RNA recognition motif) domains. IGF2BP2 binds to the 5'-UTR of the Insulin-Like Growth Factor 2 (IGF2) mRNA. This binding is isoform-specific. IGF2BP2 may regulate translation of target mRNAs. Genetic variation at the IGF2BP2 gene has been associated with type 2 diabetes (T2D) by genome-wide association studies and by replication analyses.

PIGR binds polymeric IgA and IgM at the basolateral surface of epithelial cells. The complex is then transported across the cell to be secreted at the apical surface. During this process a cleavage occurs that separates the extracellular (known as the secretory component) from the transmembrane segment.

NSMCE3 Protein, Human, Recombinant (His) is expressed in E. coli expression system with N-6xHis tag. The predicted molecular weight is 38.4 kDa and the accession number is Q96MG7.

Catalyzes the 2 serial methylation steps for the conversion of the 7-monomethylguanosine (m(7)G) caps of snRNAs and snoRNAs to a 2,2,7-trimethylguanosine (m(2,2,7)G) cap structure. The enzyme is specific for guanine, and N7 methylation must precede N2 methylation. Hypermethylation of the m7G cap of U snRNAs leads to their concentration in nuclear foci, their colocalization with coilin and the formation of canonical Cajal bodies (CBs). Plays a role in transcriptional regulation.

Interleukin (IL)-20 is a member of the IL-10 family of cytokines, which has been reported to participate in autoimmune inflammatory diseases. However, the potential role of IL-20 in hepatocellular carcinoma (HCC) progression has not yet been investigated. In addition, IL-20 expression was significantly associated with tumor size, metastasis, TNM stage and poor prognosis in patients with HCC. IL-20 Protein, Human, Recombinant (hFc) is expressed in HEK293 mammalian cells with N-hFc tag. The predicted molecular weight is 44.8 kDa and the accession number is Q9NYY1-1.

Interleukin (IL)-20 is a member of the IL-10 family of cytokines, which has been reported to participate in autoimmune inflammatory diseases. However, the potential role of IL-20 in hepatocellular carcinoma (HCC) progression has not yet been investigated. In addition, IL-20 expression was significantly associated with tumor size, metastasis, TNM stage and poor prognosis in patients with HCC. IL-20 Protein, Mouse, Recombinant (His) is expressed in HEK293 mammalian cells with N-His tag. The predicted molecular weight is 19.5 kDa and the accession number is Q9JKV9.

Artemin (ARTN) is a member of glial cell line-derived neurotrophic factor (GDNF) family of ligands, and its signaling is mediated via a multi-component receptor complex including the glycosylphosphatidylinositol-anchored GDNF family receptors a (GFRa1, GFRa3) and RET receptor tyrosine kinase. The major mechanism of ARTN action is via binding to a non-signaling co-receptor. The major function of ARTN is to drive the molecule to induce migration and axonal projection from sympathetic neurons. It also promotes the survival, proliferation and neurite outgrowth of sympathetic neurons in vitro. ARTN triggers oncogenicity and metastasis by the activation of the AKT signaling pathway. Recent studies have reported that the expression of ARTN in hepatocellular carcinoma is associated with increased tumor size, quick relapse and shorter survival. Furthermore, ARTN promotes drug resistance such as antiestrogens, doxorubicin, fulvestrant, paclitaxel, tamoxifen and trastuzumab. Moreover, ARTN also stimulates the radio-therapeutic resistance. Hypoxia has been reported to regulate the cancer stem cell (CSC) population yet the underlying mechanism is poorly characterized. Artemin (ARTN) is a member of the glial cell derived neurotrophic factor family of ligands, is a hypoxia-responsive factor and is essential for hypoxia-induced CSC expansion in hepatocellular carcinoma (HCC). Clinically, elevated expression of ARTN in HCC was associated with larger tumor size, faster relapse and shorter survival. In vitro, HCC cells with forced expression of ARTN exhibited reduced apoptosis, increased proliferation, epithelial-mesenchymal transition (EMT) and enhanced motility. Additionally, ARTN dramatically increased xenograft tumor size and metastasis in vivo. Moreover, ARTN also enhanced tumorsphere formation and the tumor initiating capacity of HCC cells, consequent to expansion of the CD133+ CSC population. ARTN transcription was directly activated by hypoxia-induced factor-1α (HIF-1α) and hypoxia induced ARTN promoted EMT and increased the CSC population via AKT signaling.

Fn14 (tumor necrosis factor receptor superfamily, member 12A), also known as TNFRSF12A, is the receptor for TNFSF12/TWEAK. Fn14 shares 82% amino acid identity with the mouse sequence. It contains a signal peptide, an extracellular domain, a membrane-anchoring domain, and a cytoplasmic domain. In response to FGF1, calf serum, or phorbol ester stimulation of human quiescent fibroblasts in vitro, the level of Fn14 is increased. A 1.2-kb FN14 transcript was expressed at high levels in heart, placenta, and kidney, at intermediate levels in lung, skeletal muscle, and pancreas, and at low levels in brain and liver. Also, elevated FN14 expression was found in human liver cancer cell lines and hepatocellular carcinoma specimens. Expression of mouse Fn14 was upregulated in hepatocellular carcinoma nodules that develop in 2 different transgenic mouse models of hepatocarcinogenesis. TNFRSF12A is the weak inducer of apoptosis in some cell types. It promotes angiogenesis and the proliferation of endothelial cells. TNFRSF12A may modulate cellular adhesion to matrix proteins.

Acetylcholinesterase, also known as ACHE, is an enzyme that degrades (through its hydrolytic activity) the neurotransmitter acetylcholine, producing choline and an acetate group. Acetylcholinesterase plays a crucial role in nerve impulse transmission at cholinergic synapses by rapid hydrolysis of the neurotransmitter acetylcholine (ACh). ACHE appears to be a potential therapeutic target at muscle injuries including organophosphate myopathy. It is an externally oriented membrane-bound enzyme and its main physiological role is termination of chemical transmission at cholinergic synapses and secretory organs by rapid hydrolysis of the neurotransmitter acetylcholine (ACh). ACHE plays important roles in the cholinergic system, and its dysregulation is involved in a variety of human diseases. ACHE was significantly down-regulated in the cancerous tissues of 69.2% of hepatocellular carcinoma (HCC) patients, and the low ACHE expression in HCC was correlated with tumor aggressiveness, an elevated risk of postoperative recurrence, and a low survival rate. Both the recombinant ACHE protein and the enhanced expression of ACHE significantly inhibited HCC cell growth in vitro and tumorigenicity in vivo. ACHE as a tumor growth suppressor in regulating cell proliferation, the relevant signaling pathways, and the drug sensitivity of HCC cells. Thus, ACHE is a promising independent prognostic predictor for HCC recurrence and the survival of HCC patients. ACHE is responsible for the hydrolysis of acetylcholine in the nervous system. It is inhibited by organophosphate and carbamate pesticides. However, this enzyme is only slightly inhibited by organophosphorothionates.

Growth Arrest and DNA Damage-Inducible Protein GADD45 β (GADD45B) is a member of the GADD45 family. GADD45B has been shown to interact with MAP3K4, ASK1, MAP2K7, and GADD45GIP1. GADD45B is involved in the regulation of growth and apoptosis. GADD45B reacts to environmental stresses by mediating activation of stress-responsive MTK1/MEKK4 kinase, which is an upstream activator of both p38 and JNK MAPKs. In addition, GADD45B participates in the down-regulation of hepatocellular carcinoma (HCC). It may serve as a possible therapeutic target.

Alpha-fetoprotein (AFP) is classified as a member of the albuminoid gene superfamily consisting of albumin, AFP, vitaminD (Gc) protein, and alpha-albumin. AFP is a major plasma protein produced by the yolk sac and the liver during fetal development. It is thought to be the fetal form of serum albumin. AFP binds to copper, nickel, fatty acids and bilirubin and is found in monomeric, dimeric and trimeric forms. AFP is one of the several embryo-specific proteins and is adominant serum protein as early in human embryonic life as one month, when albumin and transferrin are present in relatively small amounts. It is first synthesized in the human by the yolk sac and liver (1-2 months) and subsequently predominantly in the liver. A small amount of AFP is produced by the GI tract of the human conceptus. It has been proved that AFP may reappear in the serum in elevated amounts in adult life in association with normal restorative processes and with malignnt growth. Alpha-fetoprotein (AFP) is a specific marker for hepatocellular carcinoma (HCC), teratoblastomas, and neural tube defect (NTD).

SERPINB3, also known as SCCA-1, belongs to the serpin family. Serpins are a group of proteins with similar structures that were first identified as a set of proteins able to inhibit proteases. The acronym serpin was originally coined because many serpins inhibit chymotrypsin-like serine proteases. SERPINB3 is expressed in some hepatocellular carcinoma (at protein level). Its expression is closely related to cellular differentiation in both normal and malignant squamous cells. It seems to also be secreted in plasma by cancerous cells but at a low level. SERPINB3 significantly attenuates apoptosis by contrasting cytochrome c release from the mitochondria and by antichemotactic effect for NK cells. It may act as a protease inhibitor to modulate the host immune response against tumor cells and may be involved in the malignant behavior of squamous cell carcinoma cells.

Gankyrin is a multicatalytic proteinase oncoprotein consists of 7 ankyrin repeats. Gankyrin overexpressed in most hepatocellular carcinomas. Gankyrin is involved in theregulation of the phosphorylation of the retinoblastoma protein by CDK4 to enhance the ubiquitinylation of p53 by MDM2. Gankyrin is also involved in progression of esophageal squamous cell carcinoma. Gankyrin plays an oncogenic role especially in early stages of human epatocarcinogenesis.

Erythropoietin‑producing hepatocellular carcinoma cell surface type‑A receptor 3 (EPHA3) has been found to promote the proliferation and survival of prostate cancer (PCa) cell lines and prostate tumor development in nude mice. The interaction of AR and SP1 contributes to regulate EPHA3 expression, and the SP1 binding sites (‑295~‑261) in the EPHA3 core promoter region is crucial to the regulation of EPHA3 expression in response to androgen hormone stimuli.

Fibrinogen-like protein 1(FGL1) is also known as HP-041, Hepassocin, HFREP-1, LFIRE-1, is a liver-specific secreted protein belonging to the fibronogen superfamily, whose members share a fibrinogen domain at their C-termini. It is secreted by the liver and functions as a mitogen for hepatocytes. Hepassocin may play a role in the development of hepatocellular carcinomas. Hepassocin is a disulfide-linked homodimeric protein with a C-terminal fibrinogen domain. It is reported that it is a major immune inhibitory ligand of LAG-3 .

Hepatocellular carcinoma (HCC) is a major contributor to cancer-related deaths due to its often late stage diagnosis, and dermcidin (DCD) may have the potential to be used as a serum biomarker for HCC for more timely diagnoses. Human dermcidin (DCD) is an antimicrobial peptide secreted constitutively by sweat glands. And the role of DCD in ischemic heart disease has drawn increasing attention in particular its relationship with insulin secretion and glycemic control, nitric oxide (NO) synthesis and hypertension, platelet aggregation and acute myocardial infarction (AMI).

Ninjurin-1, also known as NINJ1, is a member of the Ninjurin family of transmembrane (TM) proteins. It is expressed in CD19(+) CD10(+) B-cell progenitor cells and higher levels in B-lineage acute lymphoblastic leukemia cells. Ninjurin-1 is expressed also in some other adult and embryonic tissues, predominantly in epithelial cells. Its expression is upregulated after axotomy in neurons and Schwann cells surrounding the distal nerve segment. Upregulated expression of ninjurin-1 has been identified as a marker of minimal residual disease in B-lineage acute lymphoblastic leukemia. It mediates homophilic adhesion and promotes neurite extension of dorsal root ganglion neurons in vitro. Ninjurin-1 has been found to show a high expression level in the liver tissue of patients with hepatocellular carcinoma, and this seems to be associated with cases of cirrhosis and chronic viral hepatitis. It has been reported that NINJURIN increases p21 expression and induces cellular senescence in human hepatoma cells.

KIAA11, also known as p15(PAF), is a proliferating cell nuclear antigen-associated factor that interacts with proliferating cell nuclear antigen(PCNA). It was initially isolated in a yeast two-hybrid screen for PCNA binding partners and was shown to bind PCNA competitively with the cell cycle regulator p21(WAF). KIAA11 is localized primarily in the nucleus. It shares the conserved PCNA binding motif with several other PCNA binding proteins including CDK inhibitor p21. KIAA11 is involved in cell proliferation and plays a role in early tumor recurrence (ETR), and prognosis of hepatocellular carcinoma (HCC). KIAA11 is expressed predominantly in the liver, pancreas, and placenta. It cannot be detected in the heart or brain. It is highly expressed in some tumors, especially esophageal tumors, in anaplastic thyroid carcinomas, and non-small-cell lung cancer lines. Overexpression of KIAA11 predicts high stage, early tumor recurrence, and poor prognosis of hepatocellular carcinoma. It also may be involved in the protection of cells from UV-induced cell death.

Angiopoietin-like protein 1 (ANGPTL1) has been reported to suppress migration and invasion in lung and breast cancer, acting as a novel tumor suppressor candidate. Downregulation of tumor suppressor signaling plays an important role in the pathogenesis of hepatocellular carcinoma (HCC).The downregulation of the angiopoietin-like protein ANGPTL1 is associated with vascular invasion, tumor thrombus, metastasis, and poor prognosis in HCC. Ectopic expression of ANGPTL1 in HCC cells effectively decreased their in vitro and in vivotumorigenicity, cell motility, and angiogenesis. shRNA-mediated depletion of ANGPTL1 exerted opposing effects. ANGPTL1 promoted apoptosis via inhibition of the STAT3/Bcl-2-mediated antiapoptotic pathway and decreased cell migration and invasion via downregulation of transcription factors SNAIL and SLUG. Furthermore, ANGPTL1 inhibited angiogenesis by attenuating ERK and AKT signaling and interacted with integrin α1β1 receptor to suppress the downstream FAK/Src-JAK-STAT3 signaling pathway. Taken together, these results suggest ANGPTL1 as a prognostic biomarker and novel therapeutic agent in HCC. ANGPTL1 expression was down-regulated in CRC tissues and inversely correlated with poor survival. ANGPTL1 repressed migration and invasion of CRC cells, and microRNA-138 was involved in this process. Angiopoietin-like protein 1 (ANGPTL1) has been shown to act as a tumor suppressor by inhibiting angiogenesis, cancer invasion, and metastasis.

Phosphoinositide-3-kinase-interacting protein 1(PIK3IP1) is an enzyme that in humans is encoded by the PIK3IP1 gene.It is a negative regulator of phosphatidylinositol-3-kinase (PI3K), suppresses the development of hepatocellular carcinoma. The gene encoding PIK3IP1 maps to human chromosome 22, which houses over 500 genes and is the second smallest human chromosome. Mutations in several of the genes that map to chromosome 22 are involved in the development of Phelan-McDermid syndrome, Neurofibromatosis type 2, autism and schizophrenia.

Interleukin (IL)-20 is a member of the IL-10 family of cytokines, which has been reported to participate in autoimmune inflammatory diseases. However, the potential role of IL-20 in hepatocellular carcinoma (HCC) progression has not yet been investigated. In addition, IL-20 expression was significantly associated with tumor size, metastasis, TNM stage and poor prognosis in patients with HCC. IL-20 Protein, Mouse, Recombinant (hFc) is expressed in HEK293 mammalian cells with N-hFc tag. The predicted molecular weight is 44.9 kDa and the accession number is Q9JKV9.

Single nucleotide polymorphism (SNP) of complement component 2 (C2) has been found to be significantly associated with hepatocellular carcinoma (HCC). Significantly lower C2 expression was found at HCC compared to healthy controls, and C2 was associated with TNM stages. Higher C2 expression was significantly associated with better prognosis, and multivariate analysis showed that C2 was also an independent factor for the prognosis of HCC.

Immunoglobulin superfamily member 11(IGSF11) is expressed on the plasma membrane in the testis and brain. These IGSF proteins undergo final modifications during capacitation and/or the acrosome reaction. IGSF proteins share significant homology with endothelial cell-selective adhesion molecule and coxsackievirus and adenovirus receptor, which mediates cell attachment and homotypic intercellular interactions. In clinical, the IGSF11 has been reported to overexpressed in colorectal cancers and hepatocellular carcinomas, as well as intestinal-type gastric cancers, compared to their corresponding non-cancerous tissues. The IGSF11 has also been found expressed abundantly in the testis and ovary and the IGSF11 can be used as a candidate of cancer-testis antigen.

SET and MYND domain-containing protein 3, also known as Zinc finger MYND domain-containing protein 1, SMYD3, and ZMYND, is a member of the histone-lysine methyltransferase family. SMYD3 contains one MYND-type zinc finger and one SET domain. SMYD3 is a histone H3 lysine-4-specific methyltransferase. It is expressed in skeletal muscles and testis. It is overexpressed in a majority of colorectal carcinoma (CRC) and hepatocellular carcinoma (HCC). SMYD3 plays an important role in transcriptional regulation in human carcinogenesis. It activates the transcription of a set of downstream genes. Of these downstream genes, there are several oncogenes and genes associated with cell adhesion (including those of N-Myc, CrkL, Wnt1b, L-selectin, CD31 and galectin-4), which have been shown to have effects on cell viability, adhesion, migration and metastasis. Increased SMYD3 expression is essential for the proliferation of breast cancer cells. SMYD3 may be a promising new target of therapeutic intervention for the treatment of cancers or other pathological processes associated with cell adhesion and migration.

Cytosolic beta-glucosidase, also known as Cytosolic beta-glucosidase-like protein 1, GBA3, CBG and CBGL1 is a cytoplasm protein which belongs to theglycosyl hydrolase 1 family and Klotho subfamily. GBA3 / CBGL1 is a glycosidase probably involved in the intestinal absorption and metabolism of dietary flavonoid glycosides. GBA3 / CBGL1 is present in small intestine (at protein level). GBA3 / CBGL1 is expressed in liver, small intestine, colon, spleen and kidney. GBA3 / CBGL1 is down-regulated in renal cell carcinomas and hepatocellular carcinomas. GBA3 / CBGL1 is able to hydrolyze a broad variety of glycosides including phytoestrogens, flavonols, flavones, flavanones and cyanogens. GBA3 / CBGL1 possesses beta-glycosylceramidase activity and may be involved in a nonlysosomal catabolic pathway of glycosylceramide.

Growth Arrest and DNA Damage-Inducible Protein GADD45 Υ (GADD45G) is a nuclear protein which belongs to the GADD45 family. GADD45G is highly expressed in placenta. GADD45G interacts with various proteins whose transcript levels are increased following stressful growth arrest conditions and treatment with DNA-damaging agents. GADD45G responds to environmental stresses by mediating activation of the p38/JNK pathway via MTK1/MEKK4 kinase. GADD45G is also involved in the regulation of growth and apoptosis. GADD45G inhibits cell growth and differentiation by androgens. The mRNA expression is down-regulated in hepatocellular carcinoma.

Interleukin (IL)-20 is a member of the IL-10 family of cytokines, which has been reported to participate in autoimmune inflammatory diseases. However, the potential role of IL-20 in hepatocellular carcinoma (HCC) progression has not yet been investigated. In addition, IL-20 expression was significantly associated with tumor size, metastasis, TNM stage and poor prognosis in patients with HCC. IL-20 Protein, Human, Recombinant (His) is expressed in HEK293 mammalian cells with N-His tag. The predicted molecular weight is 19.4 kDa and the accession number is Q9NYY1.

Serpin A1 is a prototype member of the Serpin superfamily of the serine protease inhibitors. As one of the most abundant proteinase inhibitors in the circulation, it is synthesized in hepatocytes, and to a lesser extent, in macrophages as well as intestinal epithelial cell lines and secreted as the abundant proteinase inhibitor in the circulation whose targets include elastase, plasmin, thrombin, trypsin, chymotrypsin, and plasminogen activator. Point mutations in the native SerpinA1 variants result in Serpin A1 deficiency, and consequently lead to several clinical complications such as pulmonary emphysema, juvenile hepatitis, cirrhosis, and hepatocellular carcinoma. For example, the Z variants (Glu342 to Lys) forms intracellular inclusion bodies, is not secreted, and leads to a severe SerpinA1 deficiency. Accordingly, Serpin A1 deficiency in circulation is associated with emphysema or liver disease.

GADD45G, also known as CR6, is part of the nuclear proteins to interact with various proteins whose transcript levels are raised after stressful growth arrest conditions and treatment with DNA-damaging agents. GADD45G reacts to environmental stresses by mediating activation of the p38/JNK pathway which is mediated through their protein binding and activating MTK1/MEKK4 kinase, which is an upstream activator of both p38 and JNK MAPKs. GADD45G acts as a new-age tumor suppressor however is being frequently inactivated epigenetically in multiple tumors. GADD45G mRNA expression is down-regulated in hepatocellular carcinoma. GADD45G causes cell cycle arrest at G2/M transition when transfected into Hep-G2 cells. GADD45G induction by androgens involves new protein synthesis. Overexpression of GADD45G inhibits cell growth and causes morphological modifications in prostate cell lines thus GADD45G takes part in differentiation induction by androgens.

Dysregulation of MST1/STK4, a key kinase component of the Hippo-YAP pathway, is linked to the etiology of many cancers with poor prognosis. STK4/Hippo pathway may have important therapeutic implications for cancer. The tumor suppressor serine/threonine-protein kinase 4 (STK4) differentially regulates TLR3/4/9-mediated inflammatory responses in macrophages and thereby is protective against chronic inflammation-associated Hepatocellular carcinoma (HCC). STK4 has potential as a diagnostic biomarker and therapeutic target for inflammation-induced HCC.