Scavenger Receptor Class A Member 5 Research Articles

Mechanism and functional verification of genes by virulence factors of P. gingivalis in ferroptosis

ObjectivePorphyromonas gingivalis (P. gingivalis) is a key etiological agent in periodontitis and functions as a facultative intracellular microorganism and involves many virulence factors. These virulence factors participate in multiple intracellular processes, like ferroptosis, the mechanistic underpinnings remain to be elucidated. Aim of this study was to investigate the effects of virulence factors on the host cells. DesignHuman umbilical vein endothelial cells (HUVECs) were treated with 4% paraformaldehyde-fixed P. gingivalis, and subsequent alterations in gene expression were profiled via RNA-seq. Further, the molecules associated with ferroptosis were quantitatively analyzed using qRT-PCR and Western blot. ResultsA total of 1125 differentially expressed genes (DEGs) were identified, encompassing 225 upregulated and 900 downregulated. Ferroptosis was conspicuously represented in the kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis, with notable upregulation of Heme oxygenase 1 (HMOX1), Ferritin light chain (FTL), and Solute carrier family 3 member 2 (SLC3A2) and downregulation of Scavenger receptor class A member 5 (SCARA5) and glutaminase (GLS). Random selection of DEGs for validation through qRT-PCR corroborated the RNA-Seq data (R2 = 0.93). Kelch like ECH associated protein 1 (Keap1) protein expression decreased after 4 and 8 h, while NFE2 like bZIP transcription factor 2 (Nrf2) and HMOX1 were elevated, with significant nuclear translocation of Nrf2. ConclusionsThe virulence factors of P. gingivalis may potentially instigating ferroptosis through activation of the Keap1-Nrf2-HMOX1 signaling cascade, in conjunction with modulating the expression of other ferroptosis-associated elements. Further research is necessary to achieve a thorough comprehension of these complex molecular interactions.

Morinda officinalis polysaccharide promotes the osteogenic differentiation of human bone marrow-derived mesenchymal stem cells via microRNA-210-3p/scavenger receptor class A member 3.

Morinda officinalis polysaccharide (MOP) is the bioactive ingredient extracted from the root of Morinda officinalis, and Morinda officinalis is applied to treat osteoporosis (OP). The purpose of this study was to determine the role of MOP on human bone marrow mesenchymal stem cells (hBMSCs) and the underlying mechanism. HBMSCs were isolated from bone marrow samples of patients with OP and treated with MOP. Quantitative real-time polymerase chain reaction was adopted to quantify the expression of microRNA-210-3p (miR-210-3p) and scavenger receptor class A member 3 (SCARA3) mRNA. Cell Counting Kit-8 assay was employed to detect cell viability; Terminal-deoxynucleotidyl Transferase Mediated Nick End Labeling assay and flow cytometry were adopted to detect apoptosis; Alkaline Phosphatase (ALP) activity assay kit was applied to detect ALP activity; Western blot was executed to quantify the expression levels of SCARA3, osteogenic and adipogenic differentiation markers. Ovariectomized rats were treated with MOP. Bone mineral density (BMD), serum tartrate-resistant acid phosphatase 5b (TRACP 5b), and N-telopeptide of type I collagen (NTx) levels were assessed by BMD detector and Enzyme-linked immunosorbent assay kits. It was revealed that MOP could promote hBMSCs' viability and osteogenic differentiation and inhibit apoptosis and adipogenic differentiation. MOP could also upregulate SCARA3 expression through repressing miR-210-3p expression. Treatment with MOP increased the BMD and decreased the TRACP 5b and NTx levels in ovariectomized rats. MOP may boost the osteogenic differentiation and inhibit adipogenic differentiation of hBMSCs by miR-210-3p/SCARA3 axis.

Paeonol upregulates expression of tumor suppressors TNNC1 and SCARA5, exerting anti-tumor activity in non-small cell lung cancer cells.

Paeonol, a naturally bioactive phenolic ingredient predominantly isolated from Paeonia suffruticosa, has recently garnered significant interest as an anti-tumor agent against diverse carcinomas including non-small cell lung cancer (NSCLC). However, the anti-tumor mechanism of paeonol in NSCLC remains unclear. Cell viability, caspase-3 activity, and apoptosis were evaluated using CCK-8 assay, Caspase-3 Colorimetric Assay Kit, and flow cytometry analysis, respectively. GSE186218 was downloaded from NCBI Gene Expression Omnibus (GEO). The common genes were screened using GEO2R and Draw Venn Diagram software. Expression of troponin C type 1 (TNNC1), scavenger receptor class A member 5 (SCARA5), phosphorylated protein kinase B (AKT) (p-AKT) and AKT was examined using GEPIA database, qRT-PCR and western blot analysis. Paeonol treatment concentration-dependently inhibited cell viability and increased caspase-3 activity and apoptotic rate in NSCLC cells. Only 5 overlapping genes including TNNC1 and SCARA5 were obtained among 232 upregulated genes in GSE186218, 200 underexpressed genes in TCGA-LUAD, and 200 underexpressed genes in TCGA-LUSC according to the Venn diagram software. TNNC1 and SCARA5, two known tumor suppressors, were significantly downregulated in LUAD and LUSC tissues and NSCLC cells. Paeonol dose-dependently upregulated TNNC1 and SCARA5 expression in NSCLC cells. Paeonol suppressed the AKT pathway by upregulating TNNC1 and SCARA5 expression. AKT inhibitor attenuated the effects of TNNC1 or SCARA5 knockdown on the anti-tumor activity of paeonol. In conclusion, paeonol exhibited anti-cancer activity in NSCLC cells through inactivating the AKT pathway by upregulating TNNC1 or SCARA5.

SCARA5 Is Overexpressed in Prostate Cancer and Linked to Poor Prognosis.

Prostate cancer is one of the most common malignancies worldwide, showing a wide range of clinical behaviors. Therefore, several treatment options arise out of the diagnosis "prostate cancer". For this reason, it is desirable to find novel prognostic and predictive markers. In former studies, we showed that THSD7A expression is associated with unfavorable prognostic parameters in prostate cancer and is linked to a high expression of focal adhesion kinase (FAK). Recently, scavenger receptor class A member 5 (SCARA5) was reported to be the downstream gene of THSD7A in esophageal squamous cell carcinoma. SCARA5 is believed to play an important role in the development and progression of several different tumor types. Most studies describe SCARA5 as a tumor suppressor. There is also evidence that SCARA 5 interacts with FAK. To examine the role of SCARA5 as a potential biomarker in prostate cancer, a total of 461 prostate cancers were analyzed via immunohistochemistry using tissue microarrays. Furthermore, we compared the expression level of SCARA5 with our previously collected data on THSD7A and FAK. High SCARA5 expression was associated with advanced tumor stage (p < 0.001), positive nodal status (p < 0.001) and high Gleason-score (p < 0.001). At least, strongly SCARA5-positive cancers were associated with THSD7A-positivity. There was no significant association between SCARA5 expression level and FAK expression level. To our knowledge, we are the first to investigate the role of SCARA5 in prostate cancer and we demonstrated that SCARA5 might be a potential biomarker in prostate cancer.

SCARA5 as a downstream factor of PCAT29, inhibits proliferation, migration, and invasion of bladder cancer

Scavenger receptor class A, member 5 (SCARA5) has been identified a novel tumor suppressor in several cancers. However, the functional and underlying mechanism of SCARA5 in bladder cancer (BC) need investigation. Here, we found SCARA5 expression was downregulated in both BC tissues and cell lines. Low SCARA5 in BC tissues was associated with a shorter overall survival. Moreover, SCARA5 overexpression reduced BC cell viability, colony formation, invasion, and migration. Further investigation demonstrated that the expression of SCARA5 was negatively regulated by miR-141. Furthermore, the long non-coding RNA prostate cancer associated transcript 29 (PCAT29) inhibited the proliferation, invasion, and migration of BC cells by sponging miR-141. Luciferase activity assays revealed that PCAT29 targeted miR-141 and miR-141 targeted SCARA5. In conclusion, SCARA5, as a downstream factor of the PCAT29/miR-141 axis, inhibited the proliferation, migration, and invasion of BC cells. These findings provide novel insights into the detailed molecular mechanisms of BC development.

SCARA5 in bone marrow stromal cell-derived exosomes inhibits colorectal cancer progression by inactivating the PI3K/Akt pathway

Colorectal cancer (CRC) is the fourth most frequently diagnosed cancer worldwide. Bone marrow stromal cells (BMSCs) play an essential role in tumor development by secreting exosomes. Scavenger receptor class A member 5 (SCARA5) is a newly identified tumor suppressor. This study aimed to investigate the effects of BMSCs-derived exosomes (BMSCs-Exos) on CRC development and to explore their regulatory mechanisms. BMSCs-Exos showed an oval-shaped, bilayer membrane structure. BMSCs-Exos inhibited growth and motility of CRC cells, while BMSCs-Exos with SCARA5 knockdown significantly promoted cell proliferation and movement. Exosomal SCARA5 also effectively suppressed colorectal tumor growth in mouse xenografts. Further analysis revealed that exosomal SCARA5 inhibited the phosphorylation of protein kinase B and phosphoinositide 3-kinase in both CRC cells and tumors. In conclusion, SCARA5 in BMSCs-Exos inhibited CRC progression by inactivating PI3K/Akt, thus suggesting the potential clinical application of SCARA5-containing BMSCs-Exos for CRC treatment.

Decreased expression of SCARA5 predicts a poor prognosis in melanoma using bioinformatics analysis.

It has been established that the scavenger receptor class A member 5 (SCARA5) functions as a tumor suppressor gene in various cancer types. To our knowledge, no comprehensive study has hitherto investigated the expression and function of SCARA5 in melanoma. This study aimed to determine the association between SCARA5 and melanoma. Analysis of SCARA5 mRNA expression was performed using The Cancer Genome Atlas (TCGA) data sets. To evaluate the clinical significance of SCARA5, the clinical data of 93 patients with melanoma were collected. The role of SCARA5 expression in prognosis was also analyzed. In this study, survival was evaluated by Kaplan-Meier analysis and compared using the log-rank test. Univariate and multivariate Cox proportional hazard regression analyses were used to identify independent predictors. The Kyoto Encyclopedia of Genes and Genomes, Gene Ontology, and gene set enrichment analysis (GSEA) were used to perform gene set functional annotations. Protein-protein interaction (PPI) networks were constructed to illustrate gene-gene interactions. The Tumor IMmune Estimation Resource (TIMER) database was used to explore the association between SCARA5 and immune infiltration levels. The results showed that the SCARA5 mRNA expression in melanoma was significantly lower than in adjacent normal skin tissue (p < 0.001). Moreover, decreased expression of SCARA5 in melanoma correlated with the tumor, node, and metastasis (TNM) stage and recurrence (p < 0.05). The overall survival (OS) was significantly higher in melanoma with high SCARA5 expression compared with low SCARA5 expression (p < 0.001). During univariate analysis, SCARA5 expression, tumor (T) stage, node (N) stage, metastasis (M) stage, and recurrence correlated with OS (p < 0.05). Further multivariate Cox regression analysis showed that SCARA5 expression (p = 0.012) could be an independent prognostic factor for OS in cutaneous malignant melanoma. GSEA analysis showed that SCARA5 was significantly enriched in various pathways, such as response to developmental biology and response to antimicrobial peptides. Correlation analysis showed a positive correlation with CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells (p < 0.05), and a negative correlation with tumor purity (p < 0.05). SCARA5 has significant potential as a prognostic biomarker and as a promising therapeutic target in melanoma. Furthermore, SCARA5 expression in melanoma is related to the level of immune infiltration.

SCARA5 inhibits oral squamous cell carcinoma via inactivating the STAT3 and PI3K/AKT signaling pathways.

Oral squamous cell carcinoma (OSCC) is a common tumor in the world. Despite the rapid development of medical care, OSCC is also accompanied by high incidence and mortality every year. Therefore, it is still necessary to continuously develop new methods or find new targets to treat OSCC. Previous research showed that scavenger receptor class A member 5 (SCARA5) was one of the potential biomarkers of OSCC, and its expression is significantly low in OSCC. This study aimed to explore the role and related molecular mechanisms of SCARA5 in OSCC. In this study, we found that the SCARA5 expression was lower in CAL-27 and SCC-9 cells than that in human normal oral epithelial keratinocytes. SCARA5 overexpression significantly inhibited cell proliferation and induced apoptosis of CAL-27 and SCC-9 cells. In addition, SCARA5 repressed OSCC cell epithelial-mesenchymal transformation (EMT), evidenced by increased E-cadherin expression and reduced N-cadherin expression. Finally, we found that SCARA5 could suppress STAT3, PI3K, and AKT phosphorylation. Therefore, SCARA5 was related to STAT3 and PI3K/AKT signaling pathways in OSCC. In conclusion, SCARA5 inhibited the proliferation and EMT and induced the apoptosis of OSCC cells through the inhibition of STAT3 and PI3K/AKT signaling pathways, thereby exerting a tumor suppressor effect.

Highly Expressing SCARA5 Promotes Proliferation and Migration of Esophageal Squamous Cell Carcinoma.

Background Thrombospondin type 1 domain-containing 7A (THSD7A) was reported to play a procancer role in esophageal squamous cell carcinoma (ESCC). The aim of the study was to screen the downstream functional genes of THSD7A and explore their functions in ESCC, based on the reported research into THSD7A function and on gene microarrays. Methods We adopted quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and Celigo high-content screening (HCS) technology to screen the downstream genes of THSD7A. The expression level of target genes was examined by PCR, western blot, and immunohistochemistry (IHC). The effects of these target genes on ESCC malignant biological behavior were performed in vivo and in vitro. The Kaplan-Meier (K-M) survival analysis and Cox regression were used to analyze the prognostic significance of target genes in ESCC patients. Experiments in the literature on liver cancer (LC) were repeated to verify the functions of these genes in different tumors. We further explored the cancer-promoting mechanism of target genes in ESCC by sequencing of the genes' exons. Results Scavenger receptor class A member 5 (SCARA5) was proved to be the downstream driving gene of THSD7A. SCARA5 promoted cell proliferation and migration but inhibited apoptosis in ESCC. IHC results confirmed that SCARA5 expression in ESCC exceeded that in normal tissues. The K-M survival analysis indicated that SCARA5 expression quantity was not related to prognosis, but tumor volume and T classification were both the independent prognostic factors. Repetition of experiments in LC in the literature confirmed that SCARA5 had exactly opposite functions in EC and LC. Conclusion SCARA5 was related to the development and occurrence of ESCC. Our findings suggested that it was a potentially diagnostic individualized therapeutic target for ESCC in the future and that its application could possibly be combined with that of upstream THSD7A gene.

Large-scale isolation of functional dermal papilla cells using novel surface marker LEPTIN Receptor.

Dermal papilla (DP) cells regulate hair follicle epithelial cells and melanocytes by secreting functional factors, playing a key role in hair follicle morphogenesis and hair growth. DP cells can reconstitute new hair follicles and induce hair regeneration, providing a potential therapeutic strategy for treating hair loss. However, current methods for isolating DP cells are either inefficient (physical microdissection) or only applied to genetically labeled mice. We systematically screened for the surface proteins specifically expressed in skin DP using mRNA expression databases. We identified two antibodies against receptors LEPTIN Receptor (LEPR ) and Scavenger Receptor Class A Member 5 (SCARA5) which could specifically label and isolate DP cells by flow cytometry from mice back skin at the growth phase. The sorted LEPR+ cells maintained the DP characteristics after culturing in vitro, expressing DP marker alkaline phosphatase and functional factors including RSPO1/2 and EDN3, the three major DP secretory factors that regulate hair follicle epithelial cells and melanocytes. Furthermore, the low-passage LEPR+ DP cells could reconstitute hair follicles on nude mice using chamber graft assay when combined with epithelial stem cells. The method of isolating functional DP cells we established here lays a solid foundation for developing DP cell-based therapy.

Machine learning-based screening of the diagnostic genes and their relationship with immune-cell infiltration in patients with lung adenocarcinoma

BackgroundLung adenocarcinoma (LUAD) is the most common type of lung cancer, and has a dismal mortality rate of 80%, mainly due to diagnosis at an advanced stage. Biomarkers with high specificity and sensitivity for the early diagnosis of LUAD are sparse. This study aimed to identify markers for the early diagnosis of LUAD.MethodsThe GSE32863 and GSE75037 data sets were standardized and merged to screen for differentially expressed genes (DEGs). Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted. The intersected DEGs from the least absolute shrinkage and selection operator (LASSO) and support vector machine (SVM) regression analyses were considered the hub genes. Then the diagnostic ability and expression of hub genes was tested in GSE63459 data set, Finally, CIBERSORT was used to analyze the correlation between the immune-infiltrating cells and hub genes.ResultsThe following 7 DEGs were intersected by the LASSO and SVM regression analyses: Locus 401286 (LOC401286), flavin-containing monooxygenase 2 (FMO2), XLKD1, Ras homolog family member J (RHOJ), scavenger receptor Class A member 5 (SCARA5), heat shock protein beta-2 (HSPB2), and serine incorporator 2 (SERINC2). The area under the receiver operating characteristic curve (AUC) of LOC401286, FMO2, XLKD1, RHOJ, SCARA5, HSPB2, and SERINC2 was 0.99, 1.00, 0.99, 1.00, 0.99, 0.99, and 0.98, respectively in the training groups. The AUC of LOC401286, FMO2, XLKD1, RHOJ, SCARA5, HSPB2, and SERINC2 was 0.97, 0.96, 0.94, 0.88, 0.85, 0.94 and 0.89, respectively in the validation group. The immune-cell infiltrations of naive B cells, memory B cells, plasma cells, naive cluster of differentiation (CD) 4 T cells, T follicular helper cells, regulatory T cells, gamma delta T cells, monocytes, M0 macrophages, M1 macrophages, resting mast cells, activated mast cells, and neutrophils were different between the normal and tumor tissues. Notably, these immune cells were correlated with the above-mentioned 7 diagnostic genes.ConclusionsWe identified 7 DEGs in LUAD tissue that can be considered diagnostic genes based on 2 machine-learning regression methods, which could be very helpful for the early diagnosis of LUAD in clinical practice.

Differential expression of circular RNA in patients with white matter hyperintensity and cognitive impairment.

White matter hyperintensity (WMH) is an important factor leading to cognitive impairment, and the mechanism has not been clarified. In recent years, studies have found that circular RNA (circRNA) has differential expression in cerebrovascular diseases. This study aims to analyze the expression profile of circRNA in peripheral blood mononuclear cell (PBMC) of patients with WMH with cognitive impairment, to screen the differentially expressed circRNA, and to explore the possible role of circRNA in WMH with cognitive impairment. CircRNA microarray was used to detect the circRNA expression profile of PBMC in patients with WMH with cognitive impairment, and in patients with WMH without cognitive impairment as well as in normal controls (3 cases each, male to female ratio of 2꞉1). The differentially expressed circRNA in patients with WMH with cognitive impairment was screened. The screening criteria for differentially expressed circRNA was fold change (FC) ≥2.0 (|log2FC ≥1) and P<0.05. TargetScan and miRanda target gene analysis software were used to predict the relevant target miRNA, and Genespring software was used to predict the target genes. Compared with the control group, there were 5 significantly up-regulated circRNA and 3 down-regulated circRNA in the WMH with cognitive impairment group; 8 circRNA were significantly up-regulated and 2 were down-regulated in the WMH without cognitive impairment group. When compared with the WMH with cognitive impairment group, no co-differentially expressed circRNA was found in WMH without cognitive impairment group and control group. Compared with the control group, the expression of hsa_circ_0092222 was up-regulated and the expressions of hsa_circ_0000662 and hsa_circ_0083773 were down-regulated in the WMH with cognitive impairment group and the WMH without cognitive impairment group, and there was no significant difference between the 2 groups (all P>0.05). Two target miRNA (hsa-miR-19a-3p and hsa-miR-19b-3p) of hsa_circ_0092222 were predicted, and the target gene was ribosomal protein S4, Y-linked 1 (RPS4Y1). Hsa_circ_0000662 predicted a target miRNA (hsa-miR-194) with axis inhibitor 1 (AXIN1) as the target gene. Hsa_circ_0083773 predicted 7 target miRNA, and the target gene was recombinant scavenger receptor class A member 3 (SCARA3). The circRNA expression profile of patients with WMH is changed significantly. The differentially expressed circRNA may be the cause of WMH; Hsa_circ_0092222, hsa_circ_0000662, and hsa_circ_0083773 may regulate the expression of target genes by targeting adsorption of the target miRNA, leading to brain white matter damage through Janus kinase 2 (JAK2)/signal transducers and activators of transcription (STAT3) signal pathway and Wnt signal pathway.There is no significant difference in circRNA expression profile between WMH with or without cognitive impairment. Cognitive impairment in patients with WMH may have other reasons.

Tumor suppressive effect of scavenger receptor class A member 5 overexpression in colorectal cancer by regulating PI3K/AKT/mTOR pathway

BackgroundColorectal cancer (CRC) exhibits high risks of morbidity and mortality.ObjectiveTo investigate the effect of scavenger receptor class A member 5 (SCRAR5) on CRC and its mechanism on modulation of cancer development.MethodsThe SCRAR5 expression in four kinds of CRC cell lines (SW620, SW480, HT29, and HCT116) was measured by quantitative PCR and western blotting, respectively. The effects of SCRAR5 abnormal expression on cell proliferation, apoptosis, and migration were analyzed by CCK-8 assay, EdU assay, colony-forming assay, flow cytometry assay, Transwell assay and wound healing assay, respectively. Meanwhile, the involvements of PI3K/AKT/mTOR pathway with the role of SCRAR5 were investigated by western blotting. Afterwards, the in vivo effects of SCRAR5 abnormal expression on CRC xenograft mice were finally investigated by evaluating tumor volume, apoptosis and Ki67 expression.ResultsSCRAR5 was lowly expressed in CRC cell lines, especially SW480 cells. Up-regulation of SCRAR5 significantly promoted cell apoptosis, reduced cell proliferation and migration in SW480 cells. Notably, SCRAR5 overexpression obviously inhibited the phosphorylation levels of PI3K, AKT, and mTOR. Reversely, SCRAR5 silence exhibited promoting effects on HT29 cells. Consistently, in vivo experiments also revealed that SCRAR5 overexpression remarkably suppressed tumor volume and Ki67 expression, as well as promoted cell apoptosis.ConclusionsOverall, up-regulating of SCRAR5 obviously inhibited CRC tumor growth in vitro and in vivo, which might be related to PI3K/AKT/mTOR pathway.

SCARA5 suppresses the proliferation and migration, and promotes the apoptosis of human retinoblastoma cells by inhibiting the PI3K/AKT pathway.

Retinoblastoma (RB) is the most common ocular malignancy that occurs during childhood. Scavenger receptor class A member 5 (SCARA5) is considered to function as an anti-oncogene in several types of malignant tumor. The present study investigated the functional role and underlying mechanism of SCARA5 in human RB cells. Reverse transcription-quantitative PCR and western blotting were used to detect the relative expression levels of SCARA5 in four human RB cell lines. In addition, transfection was performed to either knockdown or induce overexpression of SCARA5 in human RB Y79 cells. The proliferation, migration and apoptosis of RB cells was then measured by Cell Counting Kit 8 assay, 5-ethynyl-2′-deoxyuridine assay, clone formation assay, Transwell assay, Hoechst staining and TUNEL staining, respectively. Western blotting was performed to detect changes in the expression levels of key proteins involved in the PI3K/AKT and apoptotic pathways. The present study revealed that SCARA5 was expressed at lower levels in four tumorigenic human RB cell lines compared with in a human retinal pigment non-tumorigenic cell line. Functional analysis demonstrated that overexpression of SCARA5 decreased the proliferation and migration, and promoted the apoptosis of human RB cells in vitro, whereas in vivo experiments revealed a decrease in RB progression following SCARA5 overexpression. In addition, overexpression of SCARA5 inhibited phosphorylated (p)-PI3K and p-AKT expression, and knockdown of SCARA5 increased p-PI3K and p-AKT expression; however, no changes in total PI3K and AKT expression were observed. Bcl-2 exhibited similar changes in expression to those displayed by p-PI3K and p-AKT, whereas Bax and cleaved caspase-3 exhibited trends in expression that were the opposite to those shown by p-PI3K and p-AKT. In conclusion, the present results demonstrated that SCARA5 could inhibit the proliferation and promote the apoptosis of RB cell lines by suppressing the PI3K/AKT signaling pathway, thus suggesting a novel strategy for treating RB.

SCARA5 inhibits gastric cancer progression via epithelial-mesenchymal transition suppression.

Scavenger receptor class A member 5 (SCARA5) has been reported to be implicated in several types of cancer. However, its biological roles and mechanism of SCARA5 in gastric cancer (GC) have not been elucidated. In the present study, SCARA5 expression was found to be downregulated in GC which was associated with promoter methylation. The protein level of SCARA5 was negatively associated with aggressive clinicopathological characteristics, as well as poor prognosis. Moreover, SCARA5 overexpression markedly suppressed the growth, migration and invasion of GC cell lines in vitro. Furthermore, upregulation of SCARA5 inhibited gastric tumor growth and metastasis in a xenograft model. Mechanistic analysis revealed that SCARA5 suppressed the migration and invasion of GC cells via inhibiting epithelial-mesenchymal transition (EMT) and inactivating MMP-2 and MMP-9. Taken together, these results demonstrated that SCARA5 might play vital roles in the GC genesis and progression and could serve as a potential biomarker for diagnosis and therapeutic target of GC.

Identification of SCARA3 with potential roles in metabolic disorders.

Obesity is characterized by the expansion of adipose tissue which is partially modulated by adipogenesis. In the present study, we identified five differentially expressed genes by incorporating two adipogenesis-related datasets from the GEO database and their correlation with adipogenic markers. However, the role of scavenger receptor class A member 3 (SCARA3) in obesity-related disorders has been rarely reported. We found that Scara3 expression in old adipose tissue-derived mesenchymal stem cells (Ad-MSCs) was lower than it in young Ad-MSCs. Obese mice caused by deletion of the leptin receptor gene (db/db) or by a high-fat diet both showed reduced Scara3 expression in inguinal white adipose tissue. Moreover, hypermethylation of SCARA3 was observed in patients with type 2 diabetes and atherosclerosis. Data from the CTD database indicated that SCARA3 is a potential target for metabolic diseases. Mechanistically, JUN was predicted as a transcriptional factor of SCARA3 in different databases which is consistent with our further bioinformatics analysis. Collectively, our study suggested that SCARA3 is potentially associated with age-related metabolic dysfunction, which provided new insights into the pathogenesis and treatment of obesity as well as other obesity-associated metabolic complications.

Identification of SCARA5 Gene as a Potential Immune-Related Biomarker for Triple-Negative Breast Cancer by Integrated Analysis.

Triple-negative breast cancer (TNBC) refers to breast cancer without significant expression of estrogen receptor (ER), progesterone receptor (PR), or human epidermal growth factor receptor 2. We sought to identify the hub genes and find the potential progression mechanism of TNBC as well as immunotherapeutic targets. First, we screened the overlapped hub genes of Immune and Stromal, and the tumor mutation burden gene sets, as well as the The Cancer Genome Atlas (TCGA)-TNBC data set. Among these hub genes, we performed gene set enrichment analysis (GSEA) and gene set variation analysis analyses to recognize and evaluate the hub genes. Moreover, immune cell infiltration was evaluated by the CIBERSORT algorithm and single-sample GSEA. In addition, the expression and methylation of scavenger receptor class A member 5 (SCARA5) in TNBC were verified by quantitative PCR and methylation-specific PCR. Also, MTT and transwell assays were used to assess the biological function of SCARA5 in TNBC. SCARA5 and CMA1 were listed, and they mainly participated in cancer-related signaling pathways and immune-related signaling pathways. Interestingly, SCARA5 was closely associated with tumor purity and immune cell infiltration. Moreover, we found that SCARA5 was significantly downregulated and hypermethylation was in the promoter of SCARA5 in TNBC tissues. Our study showed the role of SCARA5 in proliferation and migration of TNBC, and suggested that SCARA5 can potentially serve as a candidate immunotherapy target for TNBC.

Scavenger receptor class A, member 5 is associated with thyroid cancer cell lines progression via epithelial-mesenchymal transition.

Thyroid cancer (TC) has become one of most common endocrine malignancies in recent decades. Due to gene background polymorphism, it's outcome goes quite differently in each patient. For exploring the mechanism, we performed whole transcriptome sequencing of paired papillary thyroid carcinoma (PTC) and adjacent thyroid tissues. As a result, scavenger receptor class A member 5 (SCARA5) might be a crucial anti‐oncogene associated with PTC. By RT‐qPCR, we first detected the expression of SCARA5 in PTC tissue and three type of TC cell lines. Besides, The Cancer Genome Atlas (TCGA) data were gathered to analysis the relationship between SCARA5 and clinical feature. A series of loss‐function experiments in TC cell lines (KTC‐1 and BCPAP) to investigate the function of SCARA5 in PTC. The results showed that SCARA5 expression in PTC was lower than adjacent normal tissue. And, it's consistent with the TCGA database. After analyse the correlation between SCARA5 expression and clinicopathological features in TCGA database, we discovered that downregulated SCARA5 is significantly connected age (P = .04) and tumour size (P = .032). Knockdown of SCARA5 in TC cell line could significantly increase the function of cells proliferation, colony formation, migration, and invasion. Furthermore, we also proved that SCARA5 could modulate the expression of epithelial‐mesenchymal transition‐related proteins, which influence invasion and migration. To best of our knowledge, SCARA5 is a suppressor gene which was associated with PTC and might be a potential therapeutic target in the future.Significance of the studyThyroid cancer (TC) has become one of most common endocrine malignancies in recent decades. By whole transcriptome sequencing of paired papillary thyroid carcinoma (PTC) and adjacent thyroid tissues, author discovered that scavenger receptor class A member 5 (SCARA5) might be crucial anti‐oncogene associated with PTC. Furthermore, knocking‐down of SCARA5 in TC cell line can increase the function of cells proliferation, colony formation, migration, and invasion. Author also proved that SCARA5 could modulate the expression of epithelial‐mesenchymal transition‐related proteins.

Scavenger receptor class a, member 3 is associated with severity of hand, foot, and mouth disease in a case-control study.

Hand, foot, and mouth disease (HFMD) spreads rapidly and has been recognized as a public health problem in recent years in China. Unfortunately, there is no effective vaccine or antiviral drug currently for EV71 infection. In this study, we aim to identify biomarker which are associated with for severity of EV71 infection cases using high-throughput RNA sequencing approach.RNA sequencing of samples from severe HFMD (S) patients group (n = 10) and control HFMD (C) patients group (n = 10) were performed and the results were verified by qPCR. mRNA with the highest expression level was selected to be validated in an independent cohort comprising of 45 severe EV71 infected patients and 45 control by qPCR assay.Seventeen significant differentially expressed genes were identified. Scavenger receptor class A, member 3 (SCARA3) was one of the significantly upregulated genes with the highest expression level and was selected for validation. The mean relative expression levels in severe HFMD and control HFMD patients were 10.1-fold and 5.0-fold, respectively, P value <.001.We found that SCARA3 is associated with severity of HFMD, and it may be a potential prognostic marker to predict the HFMD progression in EV71 infected patients.

CSN5 Promotes Hepatocellular Carcinoma Progression by SCARA5 Inhibition Through Suppressing β-Catenin Ubiquitination.

Increasing evidence has suggested that E3 Ubiquitin LigaseCSN5 is a newly characterized oncogene involved in various types of cancer. Scavenger receptor class A member 5 (SCARA5) is an important regulator of biological processes in cancer cells. However, the roles and relationship of CSN5 and SCARA5 in hepatocellular carcinoma (HCC) remain unclear. We used RT-PCR, Western blot, and immunohistochemistry to measure CSN5 and SCARA5 expression in HCC tissues and corresponding non-tumor tissues. The CSN5 gene was overexpressed or silenced with lentiviral vectors in HCC cells. Cell proliferation was measured using CCK8 assay. And, the cell migration and invasion were analyzed by transwell assay. We found that the expressions of CSN5 and SCARA5 are inversely correlated in HCC tissues, and CSN5 expression levels were negatively correlated with the levels of SCARA5 in various HCC cells. Furthermore, we found that high level of CSN5 expression correlated closely with tumor TNM stage, tumor size, and venous metastasis, but low level of SCARA5 expression correlated closely with tumor TNM stage, tumor size, and venous metastasis. Additionally, survival of patients with lower expression of CNS5 was significantly better than that of higher expression group, but the survival of patients with higher expression of SCARA5 was significantly better than that of lower expression group. Moreover, knockdown of CSN5 increased SCARA5 expression and inhibited the proliferation and metastasis of HCC cells in vitro and in vivo. Finally, we found that CSN5 regulated SCARA5 expression by modulating β-catenin. Mechanistically, our results indicate that CSN5 can decrease β-catenin ubiquitination to enhance the protein expression of SCARA5 in HCC cells. Our data identified CSN5 as a critical oncoprotein involved in progression of HCC cells, which could serve as a potential therapeutic target in HCC patients.