HIF-1α participates in the regulation of S100A16-HRD1-GSK3ß/CK1α pathway in renal hypoxia injury.

S100 calcium-binding protein 16 (S100A16) is implicated in both chronic kidney disease (CKD) and acute kidney injury (AKI). Previous research has shown that S100A16 contributes to AKI by facilitating the ubiquitylation and degradation of glycogen synthase kinase 3ß (GSK3ß) and casein kinase 1α (CK1α) through the activation of HMG-CoA reductase degradation protein 1 (HRD1). However, the mechanisms governing S100A16-induced HRD1 activation and the upregulation of S100A16 expression in renal injury are not fully understood. In this study, we observed elevated expression of Hypoxia-inducible Factor 1-alpha (HIF-1α) in the kidneys of mice subjected to ischemia-reperfusion injury (IRI). S100A16 deletion attenuated the increased HIF-1α expression induced by IRI. Using a S100A16 knockout rat renal tubular epithelial cell line (NRK-52E cells), we found that S100A16 knockout effectively mitigated apoptosis during hypoxic reoxygenation (H/R) and cell injury induced by TGF-ß1. Our results revealed that H/R injuries increased both protein and mRNA levels of HIF-1α and HRD1 in renal tubular cells. S100A16 knockout reversed the expressions of HIF-1α and HRD1 under H/R conditions. Conversely, S100A16 overexpression in NRK-52E cells elevated HIF-1α and HRD1 levels. HIF-1α overexpression increased HRD1 and ß-catenin while decreasing GSK-3ß. HIF-1α inhibition restored HRD1 and ß-catenin upregulation and GSK-3ß downregulation by cellular H/R injury. Notably, Chromatin immunoprecipitation (ChIP) and luciferase reporter assays demonstrated HIF-1α binding signals on the HRD1 promoter, and luciferase reporter gene assays confirmed HIF-1α's transcriptional regulation of HRD1. Additionally, we identified Transcription Factor AP-2 Beta (TFAP2B) as the upregulator of S100A16. ChIP and luciferase reporter assays confirmed TFAP2B as a transcription factor for S100A16. In summary, this study identifies TFAP2B as the transcription factor for S100A16 and demonstrates HIF-1α regulation of HRD1 transcription within the S100A16-HRD1-GSK3ß/CK1α pathway during renal hypoxia injury. These findings provide crucial insights into the molecular mechanisms of kidney injury, offering potential avenues for therapeutic intervention.

BRD4L cooperates with MYC to block local tumor invasion via suppression of S100A10.

Targeted therapy based on BRD4 and MYC shows promise due to their well-researched oncogenic functions in cancer, but their tumor-suppressive roles are less understood. In this study, we employ a systematic approach to delete exons that encode the low-complexity domain (LCD) of BRD4L in cells by using CRISPR-Cas9. In particular, the deletion of exon 14 (BRD4-E14) results in cellular morphological changes towards spindle-shaped and loosely packed. BRD4-E14 deficient cells show increased cell migration and reduced cell adhesion. The expression of S100A10 was significantly increased in cells lacking E14. BRD4L binds with MYC via the E14-encoded region of the LCD to inhibit the expression of S100A10. In cancer tissues, there is a positive correlation between BRD4 and MYC, while both of these proteins are negatively associated with S100A10 expression. Finally, knocking out the BRD4-E14 region or MYC promotes tumor growth in vivo. Together, these data support a tumor-suppressive role of BRD4L and MYC in some contexts. This discovery emphasizes the significance of a discreetly design and precise patient recruitment in clinical trials that testing cancer therapy based BRD4 and MYC.

Study on the mechanism of S100A4-mediated cancer oncogenesis in uveal melanoma cells through the integration of bioinformatics and in vitro experiments.

BACKGROUND: The elevated metastasis rate of uveal melanoma (UM) is intricately correlated with patient prognosis, significantly affecting the quality of life. S100 calcium-binding protein A4 (S100A4) has tumorigenic properties; therefore, the present study investigated the impact of S100A4 on UM cell proliferation, apoptosis, migration, and invasion using bioinformatics and in vitro experiments. METHODS: Bioinformatic analysis was used to screen S100A4 as a hub gene and predict its possible mechanism in UM cells, and the S100A4 silencing cell line was constructed. The impact of S100A4 silencing on the proliferative ability of UM cells was detected using the Cell Counting Kit-8 and colony formation assays. Annexin V-FITC/PI double fluorescence and Hoechst 33342 staining were used to observe the effects of apoptosis on UM cells. The effect of S100A4 silencing on the migratory and invasive capabilities of UM cells was assessed using wound healing and Transwell assays. Western blotting was used to detect the expression of related proteins. RESULTS: The present study found that S100A4 is a biomarker of UM, and its high expression is related to poor prognosis. After constructing the S100A4 silencing cell line, cell viability, clone number, proliferating cell nuclear antigen, X-linked inhibitor of apoptosis protein, and survivin expression were decreased in UM cells. The cell apoptosis rate and relative fluorescence intensity increased, accompanied by increased levels of Bax and caspase-3 and decreased levels of Bcl-2. Additionally, a decrease in the cell migration index and relative invasion rate was observed with increased E-cadherin expression and decreased N-cadherin and vimentin protein expression. CONCLUSION: S100A4 silencing can inhibit the proliferation, migration, and invasion and synchronously induces apoptosis in UM cells.

Downregulation of S100A11 promotes T cell infiltration by regulating cancer-associated fibroblasts in prostate cancer.

OBJECTIVE: This study aims at revealing the relationship between S100A11 and cancer-associated fibroblasts (CAFs) in prostate cancer and improving T cell infiltration into solid tumors. METHODS: H&E, IHC and Sirius red staining were used to detect the stroma content in prostate cancer tissues. Stable S100A11 knockdown cell lines DU 145, 22Rv1, RM-1 and NOR-10 were established by lentivirus transfection. Co-culture system of RM-1 and CAFs was established. CCK-8, wound healing and transwell were proceeded to determine proliferation, migration and invasion of prostate cancer cells. Stably knocked-down RM-1 and CAFs were co-injected into C57BL/6 mice to detect the role of S100A11 in vivo. CAFs, CD4+ T cell and CD8+ T cell in these tumors were assessed by IF. T cell profile was analyzed by flow cytometry. RESULTS: A significant amount of stroma exists in prostate cancer tissues. Downregulation of S100A11 inhibits proliferation, migration and invasion of human prostate cancer cells in vitro, and suppresses the expression of cancer-associated fibroblasts (CAFs) in vivo. Knockdown of S100A11 enhances the inhibitory effect of Erdafitinib on CAFs in both the co-culture system and in vivo. The combined knockdown of S100A11 in tumor cells and CAFs shows a superior therapeutic effect compared to the individual knockdown in tumor cells alone. Knockdown of S100A11, both in RM-1 and CAFs, combined with Erdafitinib treatment reduces tumorigenicity by suppressing the content of CAFs and increasing the infiltration of CD4+ T cell and effective CD8+ T cell in tumor. CONCLUSION: Downregulation of S100A11 plays a crucial role in enhancing the therapeutic response to Erdafitinib and reversing immunosuppressive tumor microenvironment.

S100A11 promotes focal adhesion disassembly via myosin II-driven contractility and Piezo1-mediated Ca2+ entry.

S100A11 is a small Ca2+-activatable protein known to localize along stress fibers (SFs). Analyzing S100A11 localization in HeLa and U2OS cells further revealed S100A11 enrichment at focal adhesions (FAs). Strikingly, S100A11 levels at FAs increased sharply, yet transiently, just before FA disassembly. Elevating intracellular Ca2+ levels with ionomycin stimulated both S100A11 recruitment and subsequent FA disassembly. However, pre-incubation with the non-muscle myosin II (NMII) inhibitor blebbistatin or with an inhibitor of the stretch-activatable Ca2+ channel Piezo1 suppressed S100A11 recruitment, implicating S100A11 in an actomyosin-driven FA recruitment mechanism involving Piezo1-dependent Ca2+ influx. Applying external forces on peripheral FAs likewise recruited S100A11 to FAs even if NMII activity was inhibited, corroborating the mechanosensitive recruitment mechanism of S100A11. However, extracellular Ca2+ and Piezo1 function were indispensable, indicating that NMII contraction forces act upstream of Piezo1-mediated Ca2+ influx, in turn leading to S100A11 activation and FA recruitment. S100A11-knockout cells display enlarged FAs and had delayed FA disassembly during cell membrane retraction, consistent with impaired FA turnover in these cells. Our results thus demonstrate a novel function for S100A11 in promoting actomyosin contractility-driven FA disassembly.

Novel ATG7::RAF1 gene fusion in malignant glomus tumor.

Glomus tumors are classified as members of the perivascular myoid family of tumors. Nearly half of these show NOTCH-gene fusions and a smaller subset has BRAF V600E mutations. Here, we report a novel ATG7::RAF1 fusion in malignant glomus tumor occurring in a 40-year-old female which has not been reported in the malignant glomus tumor before. A 40-year-old female presented with a persistent lateral heel pain and an increase in the size of a mass along the lateral ankle for nearly 10 years. Resected specimen showed a well circumscribed lesion composed of spindled and epithelioid cells with moderate nuclear atypia and mitotic figures (7/10 high-power fields) including atypical forms without any necrosis, lymphovascular, or perineural invasion. The tumor was positive for smooth muscle actin, smooth muscle myosin heavy chain, H-caldesmon, collagen type IV, and discovered on gastronintestinal stromal tumors-1 but negative for AE1/3, desmin, S-100, CD34, and CD117. RNA sequencing showed presence of ATG7-RAF1 fusion. This fusion has not been reported in the malignant glomus tumor before. Future studies on larger cohorts are needed to ascertain the biological significance of these tumors with novel gene fusions.

Multi-omics Analysis Identifies Hypoxia Subtypes and S100A2 as an Immunosuppressive Factor in Cervical Cancer.

Cervical cancer is a common gynecological oncology. Growing evidence indicates hypoxia plays an important role in tumor progression and immunity. However, no study has examined the hypoxia landscape in cervical cancer. In this study, using hierarchical clustering, we identified three hypoxia subtypes in cervical cancer samples from The Cancer Genome Atlas dataset according to formerly described hypoxia-related genes. The overall survival time, hypoxic features, genomics, and immunological characteristics of these subtypes existed distinct differences. We also created a hypoxia score by principle component analysis for dimension reduction. The hypoxiaScore was an effective prognostic biomarker validated by GSE44001 and was associated with immunotherapy response. Furthermore, combined with single-cell RNA-sequence (scRNA-seq) and experiments, S100A2 was identified as an immunosuppressive factor induced by hypoxia and regulated expression of PD-L1. S100A2 also served as an oncogene promoting the proliferation and migration of cervical cancer cells. These findings depicted a new hypoxia-based classification and identified S100A2 as a potential therapeutic target for cervical cancer, thereby advancing the understanding of immunotherapy resistance mechanisms and cervical cancer genetic markers.

Unmasking the Hypoxia Landscape in Cervical Cancer: S100A2 and Its Implication for Immunotherapy Resistance.

Cervical cancer is the fourth most common cancer in women worldwide and typically diagnosed between the ages of 35 and 44. Despite the death rate declining 1% each year since the 2000s, the 5-year survival of late stage remains lower than 20%. This emphasizes the urgency to keep exploring cervical cancer cell survival factors and identifying new prognostic markers. In this issue of Reproductive Sciences, Yang et al. stratified hypoxia subtype by analyzing 200 hypoxia-related genes in TCGA database and observed patient overall survival, hypoxic, transcriptome, genomics, and immunological characteristics vary among these hypoxia subtypes and created a hypoxia score which successfully stratified patient by predicting clinical outcomes and response to immunotherapy. Simultaneously, a hypoxia mediator (S100A2) associated with an aggressive cervical cancer phenotype is identified. We reviewed similar work on S100A2 and hypoxia-mediated multidrug resistance and highlighted the values added by this study. Future work could focus on unraveling the direct link between S100A2 and immunotherapy resistance.

Roles of S100A8, S100A9 and S100A12 in infection, inflammation and immunity.

S100 proteins are small proteins that are only expressed in vertebrates. They are widely expressed in many different cell types and are involved in the regulation of calcium homeostasis, glucose metabolism, cell proliferation, apoptosis, inflammation and tumorigenesis. As members of the S100 protein subfamily of myeloid-related proteins, S100A8, S100A9 and S100A12 play a crucial role in resisting microbial infection and maintaining immune homeostasis. These proteins chelate the necessary metal nutrients of pathogens invading the host by means of 'nutritional immunity' and directly inhibit the growth of pathogens in the host. They interact with receptors on the cell surface to initiate inflammatory signal transduction, induce cytokine expression and participate in the inflammatory response and immune regulation. Furthermore, the increased content of these proteins during the pathological process makes them useful as disease markers for screening and detecting related diseases. This article summarizes the structure and function of the proteins S100A8, S100A9 and S100A12 and lays the foundation for further understanding their roles in infection, immunity and inflammation, as well as their potential applications in the prevention and treatment of infectious diseases.

Exploring the prognostic value of S100A11 and its association with immune infiltration in breast cancer.

Breast cancer (BC) is a severe danger to women's lives and health globally. S100A11 is aberrantly expressed in many carcinomas and serves a crucial function in cancer development. However, the role of S100A11 in BC is unclear. In this study, we utilized multiple databases and online tools, including the TCGA database, cBioPortal, and STRING, to evaluate the significance of S100A11 in BC prognosis and immune infiltration. We found that S100A11 was considerably more abundant in BC tissues. Survival analysis indicated that individuals with S100A11 high expression of BC had shorter overall survival. Multivariate Cox regression analysis revealed that high S100A11 expression independently influenced the poor outcome of patients with BC (HR = 1.738, 95%CI 1.197-2.524). Our nomogram incorporating five factors, including S100A11, age, clinical stage, N, and M, was developed to anticipate the survival probability in BC prognosis. The model demonstrated good consistency and accuracy. Furthermore, the mutation rete of S100A11 was 14%. Survival analysis suggested that breast cancer patients with S100A11 mutation had a worse prognosis. KEGG pathway enrichment analysis revealed that S100A11 may be mainly involved in the IL-17 signaling pathway. Finally, we discovered a correlation between S100A11 expression and immune cell infiltration on BC. S100A11 expression was positively associated with 17 immune checkpoint-related genes. In conclusion, this study indicates that S100A11 may contribute to a worse prognosis for BC and potentially has a significant impact through its influence on immune cell infiltration and the IL-17 signaling pathway.

Expression and gene regulatory network of S100A16 protein in cervical cancer cells based on data mining.

S100A16 protein belongs to the S100 family of calcium-binding proteins, which is widely distributed in human tissues and highly conserved. S100 calcium-binding proteins possess broad biological functions, such as cancer cell proliferation, apoptosis, tumor metastasis, and inflammation (Nat Rev Cancer 15:96-109, 2015). The S100A16 protein was initially isolated from a cell line derived from astrocytoma. The S100A16 protein, consisting of 103 amino acids, is a small acidic protein with a molecular weight of 11,801.4 Da and an isoelectric point (pI) of 6.28 (Biochem Biophys Res Commun 313:237-244, 2004). This protein exhibits high conservation among mammals and is widely expressed in various human tissues (Biochem Biophys Res Commun 322:1111-1122, 2004). Like other S100 proteins, S100A16 contains two EF-hand motifs that form a helix-loop-helix structural domain. The N-terminal domain and the C-terminal domain of S100A16 are connected by a "hinge" linker.S100A16 protein exhibits distinct characteristics that distinguish it from other S100 proteins. A notable feature is the presence of a single functional Ca2 + binding site located in the C-terminal EF-hand, consisting of 12 amino acids per protein monomer (J Biol Chem 281:38905-38917, 2006). In contrast, the N-terminal EF-hand of S100A16 comprises 15 amino acids instead of the typical 14, and it lacks the conserved glutamate residue at the final position. This unique attribute may contribute to the impaired Ca2 + binding capability in the N-terminal region (J Biol Chem 281:38905-38917, 2006). Studies have shown an integral role of S100 calcium-binding proteins in the diagnosis, treatment, and prognosis of certain diseases (Cancers 12:2037, 2020). Abnormal expression of S100A16 protein is implicated in the progression of breast and prostate cancer, but an inhibitor of oral cancer and acute lymphoblastic leukemia tumor cell proliferation (BMC Cancer 15:53, 2015; BMC Cancer 15:631, 2015). Tu et al. (Front Cell Dev Biol 9:645641, 2021) indicate that the overexpression of S100A16 mRNA in cervical cancer(CC) such as cervical squamous cell carcinoma and endocervical adenocarcinoma as compared to the control specimens. Tomiyama N. and co-workers (Oncol Lett 15:9929-9933, 2018) (Tomiyama, N) investigated the role of S100A16 in cancer stem cells using Yumoto cells (a CC cell line),The authors found upregulation of S100A16 in Yumoto cells following sphere formation as compared to monolayer culture.Despite a certain degree of understanding, the exact biological function of S100A16 in CC is still unclear. This article explores the role of S100A16 in CC through a bioinformatics analysis. Referencing the mRNA expression and SNP data of cervical cancer available through The Cancer Genome Atlas (TCGA) database, we analyzed S100A16 and its associated regulatory gene expression network in cervical cancer. We further screened genes co-expressed with S100A16 to hypothesize their function and relationship to the S100A16 cervical cancer phenotype.Our results showed that data mining can effectively elucidate the expression and gene regulatory network of S100A16 in cervical cancer, laying the foundation for further investigations into S100A16 cervical tumorigenesis.

Mechanism of LEF1-AS1 regulating HUVEC cells by targeting miR-489-3p/S100A11 axis.

Background: The venous malformation is the most common congenital vascular malformation and exhibits the characteristics of local invasion and lifelong progressive development. Long noncoding RNA (lncRNA) regulates endothelial cells, vascular smooth muscle cells, macrophages, vascular inflammation, and metabolism and also affects the development of venous malformations. This study aimed to elucidate the role of the lncRNA LEF1-AS1 in the development of venous malformations and examine the interaction among LEF1-AS1, miR-489-3p, and S100A11 in HUVEC cells. Methods: Venous malformation tissues, corresponding normal venous tissues, and HUVEC cells were used. Agilent human lncRNA microarray gene chip was used to screen differential genes, RNA expression was detected using quantitative reverse transcription PCR, and protein expression was detected using Western blotting. The proliferation, migration, and angiogenesis of HUVEC cells were assessed using CCK8, transwell, and in vitro angiogenesis tests. Results: A total of 1,651 lncRNAs were screened using gene chip analysis, of which 1015 were upregulated and 636 were downregulated. The lncRNA LEF1-AS1 was upregulated with an obvious difference multiple, and the fold-change value was 11.03273. The results of the analysis performed using the StarBase bioinformatics prediction website showed that LEF1-AS1 and miR-489-3p possessed complementary binding sites and that miR-489-3p and S100A11 also had complementary binding sites. The findings of tissue experiments revealed that the expressions of LEF1-AS1 and S100A11 were higher in tissues with venous malformations than in normal tissues, whereas the expression of miR-489-3p was lower in venous malformations than in normal tissues. Cell culture experiments indicated that LEF1-AS1 promoted the proliferation, migration, and angiogenesis of HUVEC cells. In these cells, LEF1-AS1 targeted miR-489-3p, which in turn targeted S100A11. LEF1-AS1 acted as a competitive endogenous RNA and promoted the expression of S100A11 by competitively binding to miR-489-3p and enhancing the proliferation, migration, and angiogenesis of HUVEC cells. Thus, LEF1-AS1 participated in the occurrence and development of venous malformation. Conclusions: The expression of LEF1-AS1 was upregulated in venous malformations, and the expression of S100A11 was increased by the adsorption of miR-489-3p to venous endothelial cells, thus enhancing the proliferation, migration, and angiogenesis of HUVEC cells. In conclusion, LEF1-AS1 is involved in the occurrence and development of venous malformations by regulating the miR-489-3p/S100A11 axis, which provides valuable insights into the pathogenesis of this disease and opens new avenues for its treatment.

Expression of S100A16 Is Associated with Biological Aggressiveness and Poor Prognosis in Patients with Bladder Cancer Who Underwent Radical Cystectomy.

S100 calcium binding protein A16 (S100A16) is expressed in various cancers; however, there are few reports on S100A16 in bladder cancer (BC). We retrospectively investigated clinical data including clinicopathological features in 121 patients with BC who underwent radical cystectomy (RC). Immunohistochemical staining was performed to evaluate S100A16 expression in archived specimens. Cases with >5% expression and more than moderate staining intensity on cancer cells were considered positive. S100A16 expression was observed in 54 patients (44.6%). Univariate analysis showed that S100A16 expression was significantly associated with age, pT stage, recurrence, and cancer-specific death. Kaplan-Meier analyses showed that patients with S100A16 expression had shorter overall survival (OS), cancer-specific survival (CSS), and recurrence-free survival (RFS) than those without S100A16 expression. In multivariate analysis, pT stage was an independent prognostic factor for OS and lymph node metastasis for CSS and RFS. S100A16 expression may be a biomarker of a biologically aggressive phenotype and poor prognosis in patients with BC who underwent RC. The PI3k/Akt signaling pathway is probably associated with S100A16 and may be a therapeutic target.

Pseudogenization of the Hair-Related Genes PADI3 and S100A3 in Cetaceans and Hippopotamus amphibius.

Hair-related genes in mammals play important roles in the development and maintenance of hair and other keratinous structures in mammals. The peptidyl arginine deiminase 3 (PADI3) gene encodes an enzyme that catalyzes the conversion of arginine residues to citrulline. The S100 calcium binding protein A3 (S100A3) gene encodes a protein that is highly expressed in the hair cuticle and contains arginine residues that are converted to citrullines by PADI enzymes. In this study, we investigated the pseudogenization events of PADI3 and S100A3 in cetaceans and Hippopotamus amphibius. We found that PADI3 underwent three independent pseudogenization events during cetacean evolution, in baleen whales, toothed cetaceans other than Physeter catodon, and P. catodon. Notably, the entire PADI3 gene is absent in the baleen whales. Pseudogenization of S100A3 occurred independently in cetaceans and H. amphibius. Interestingly, we found that in cetaceans S100A3 underwent pseudogenization before PADI3, suggesting that differential selection pressures were acting on the two genes. Our findings provide valuable insights into the molecular evolution of these genes in cetaceans and hippopotamuses, highlighting their importance for understanding the evolution of hair-related genes.

Comparative analysis of the physical properties of murine and human S100A7: Insight into why zinc piracy is mediated by human but not murine S100A7.

S100 proteins are a subfamily of EF-hand calcium-binding proteins found primarily in vertebrate animals. They are distinguished by binding of transition metals and functioning in both the intracellular and extracellular milieu. S100A7 functions in the protection of the skin and mucous membranes and is a biomarker in inflammatory skin disease. A recent study of Neisseria gonorrhoeae infection revealed that human but not murine S100A7 could be used to evade host nutritional immunity. To understand the molecular basis for this difference, we carried out a comparative analysis of the physical and structural properties of human and murine S100A7. The X-ray crystal structure of Ca2+-loaded mouse S100A7 (mS100A7) was determined to 1.69 Å resolution, and Ca2+-induced conformational changes were assessed by NMR. Unlike human S100A7 (hS100A7), which exhibits conformational changes in response to binding of Ca2+, no significant changes in mS100A7 were detected. Dynamic light scattering, circular dichroism, and a competition chelator assay were used to compare the Zn2+ affinity and the effects of ion binding on mS100A7 versus hS100A7. Alignment of their sequences revealed a substantial difference in the C-terminal region, which is an important mediator of protein-protein interactions, suggesting a rationale for the specificity of N. gonorrhoeae for hS100A7. These data, along with more detailed analysis of S100A7 sequence conservation across different species, support the proposal that, although hS100A7 is highly conserved in many mammals, the murine protein is a distinct ortholog. Our results highlight the potential limitations of using mouse models for studying bacterial infections in humans.

S100s and HMGB1 Crosstalk in Pancreatic Cancer Tumors.

Pancreatic cancer remains a disease that is very difficult to treat. S100 proteins are small calcium binding proteins with diverse intra- and extracellular functions that modulate different aspects of tumorigenesis, including tumor growth and metastasis. High mobility group box 1 (HMGB1) protein is a multifaceted protein that also actively influences the development and progression of tumors. In this study, we investigate the possible correlations, at the transcript level, between S100s and HMGB1 in pancreatic cancer. For this purpose, we calculated Pearson's correlations between the transcript levels of 13 cancer-related S100 genes and HMGB1 in a cDNA array containing 19 pancreatic cancer tumor samples, and in 8 human pancreatic cancer cell lines. Statistically significant positive correlations were found in 5.5% (5 out of 91) and 37.4% (34 of 91) of the possible S100/S100 or S100/HMGB1 pairs in cells and tumors, respectively. Our data suggest that many S100 proteins crosstalk in pancreatic tumors either with other members of the S100 family, or with HMGB1. These newly observed interdependencies may be used to further the characterization of pancreatic tumors based on S100 and HMGB1 transcription profiles.

Tailored modulation of S100A1 and RASSF8 expression by butanediamide augments healing of rotator cuff tears.

Objectives: This investigation sought to elucidate promising treatment modalities for rotator cuff tears (RCTs) by delving into the molecular machinations instigating the affliction. The focus was on differentially expressed genes (DEGs) linked to RCTs, and the exploration of their roles and operative pathways. Methods: DEGs were discerned from GEO datasets, followed by the establishment of a protein-protein interaction (PPI) network. Subsequently, the network's core genes were determined employing a Venn diagram. Enrichment analysis facilitated the unveiling of the biological roles and signal transduction pathways of these pivotal genes, thus shedding light on molecular strategies for RCT-targeted treatment. The Discovery Studio 2019 software was employed to sift through FDA-sanctioned drugs targeting these essential proteins. Moreover, the efficaciousness of these FDA-endorsed drugs vis-à-vis RCTs was corroborated by the construction of an in vivo animal model of the injury and the in vitro cultivation of tendon-derived stem cells. Results: Bioinformatics outcomes revealed a significant overexpression of S100A1 and RASSF8 in RCT patients. The FDA drug repository indicated that Butanediamide has a selective affinity for S100A1 and RASSF8. Subsequent in vivo and in vitro experimentation demonstrated that Butanediamide could suppress S100A1 expression and bolster TDSC proliferation, thereby facilitating RCT healing. Conclusions: S100A1 and RASSF8 are pivotal genes implicated in RCTs, and their roles have been elucidated. The FDA-approved compound, Butanediamide, may represent a prospective therapeutic agent for RCTs by targeting S100A1 and RASSF8, respectively.

An Update on S100A16 in Human Cancer.

S100A16 is a member of the S100 protein family. S100A16 is expressed in a variety of human tissues, although at varying levels. S100A16 expression is especially high in tissues rich in epithelial cells. mRNA and protein levels of S100A16 have been reported to be differentially expressed in the majority of human cancers. Functionally, S100A16 has been linked to several aspects of tumorigenesis, for example, cell proliferation, differentiation, migration, invasion, and epithelial-mesenchymal transition (EMT). Accordingly, S100A16 has been suggested to have both tumour-promoting and suppressive roles in human cancers. S100A16-mediated cellular functions are suggested to be mediated by the regulation of various signaling pathways/proteins including EMT-related proteins E-cadherin and Vimentin, PI3K-AKT, p53, MMP1-1, MMP-2, MMP-9, JNK/p38, etc. In addition to the functional roles, expression of S100A16 has been suggested to have prognostic potential in various cancer types. The aims of this review are to summarise the expression profile, identify common molecular partners and functional roles, and explore the prognostic potential of S100A16 in human cancers.