C1GALT1-mediated O-glycan T antigen increase enhances the migration and invasion ability of gastric cancer cells.

Gastric cancer (GC) is one of the most aggressive and lethal diseases in the world. Cancer metastasis is the mainly leading cause of death in GC patients. Aberrant Protein O-glycosylation is closely associated with tumor occurrence and metastasis. However, the effect of aberrant O-glycosylation on the progress of GC is not completely clear. This study aimed to investigate the biological function and its underlying effects mechanism of core 1 ß 1, 3-galactosyltransferase 1 (C1GALT1) C1GALT1-mediated O-glycan T antigen on GC progress. We conducted data mining analysis that C1GALT1 was obviously up-regulated in GC tissues than in para-carcinoma tissues. Elevated expression of C1GALT1 was closely associated with advanced TNM stage, lymph node metastasis, histological grade, and poor overall survival. In addition, C1GALT1 overexpression could promote GC cell proliferation, migration, and invasion, which was due to C1GALT1 overexpression-mediated O-glycan T antigen increase. Moreover, MUC1 was predicted to be a new downstream target of C1GALT1, which may be abnormally O-glycosylated by C1GALT1 thereby activating the cell adhesion signaling pathway. In conclusion, our studies proved that C1GALT1-mediated O-glycosylation increase could promote the metastasis of gastric cancer cells. These discoveries hint that C1GALT1 may serve as a novel therapeutic target for GC treatment.

Characterization of glucose-binding proteins isolated from health volunteers and human type 2 diabetes mellitus patients.

Glucose is one of the most important monosaccharides. Although hyperglycemia in type 2 diabetes mellitus (T2DM) lead to a series of changes; however, little is known about the alterations of serum proteins in T2DM, especially those proteins with glucose affinity. In this study, the glucose-binding proteins (GlcBPs) of serum were isolated from 30 health volunteer (HV) and 30 T2DM patients by glucose-magnetic particle conjugates (GMPC) and identified by mass spectrum analysis. Gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) indicated the main gene annotations and pathways of this GlcBPs, while Motif-X webtool provided the potential glucose-binding domains. Further docking analysis and glycan microarray were used to understand the interaction between the glucose and glucose-binding domains. A total of 149 and 119 GlcBPs were identified from HV and T2DM cases. Four hundred and sixty-eight GO annotations in 165 identified GlcBPs were available, while the majority involved in cellular processes and binding function. A short peptide, EGDEEITCLNGFWLE, which was derived from the Motif-X analysis, presented a high-binding ability to the glucose from both docking analysis and glycan analysis. GMPC provides a powerful tool for GlcBPs isolation and indicates the alteration of GlcBPs in T2DM.

Photoacoustic-ultrasonic dual-mode microscopy with local speed-of-sound estimation.

Synthetic aperture imaging and virtual point detection have been exploited to extend the depth of view of photoacoustic microscopy. The approach is commonly based on a constant assumed sound speed, which reduces image quality. We propose a new, to the best of our knowledge, self-adaptive technique to estimate the speed of sound when integrated with this hybrid strategy. It is accomplished through linear regression between the square of time of flight detected at individual virtual detectors and the square of their horizontal distances on the focal plane. The imaging results show our proposed method can significantly improve the lateral resolution, imaging intensity, and spatial precision for inhomogeneous tissue.

Artifact-free imaging through a bone-like layer by using an ultrasonic-guided photoacoustic microscopy.

Reflection artifacts caused by a bone-like layer badly degrade the quality of photoacoustic images in many biomedical applications, e.g., in vivo brain imaging through the skull. We proposed an ultrasonic-guided photoacoustic microscopy (PAM) to remove the reflection artifacts. This system is developed from dual-mode microscopy, integrating a scanning acoustic microscopy with a conventional PAM. Based on similar propagation characteristics of a photoacoustic signal and ultrasonic echo in a bone-like layer, we employ the ultrasonic echo as a filter to remove the multiple reflected artifacts in photoacoustic signals and obtain artifact-free images. An experiment of imaging a phantom below a bone-like film is used to demonstrate the performance of this method. The results suggest that this method can achieve an artifact-free image of the phantom under the film successfully, whereas the conventional PAM fails to achieve clean images of the vessel-like absorbers. This study might improve the imaging quality of PAM in many biomedical applications.

Effect of sodium chloride concentration on off-flavor removal correlated to glucosinolate degradation and red radish anthocyanin stability.

Anthocyanin-rich concentrates from different red radish can be used as natural food colorants. However, the development of off-flavor during extraction has been major challenge in processing industries. This work aimed to evaluate the effect of sodium chloride (NaCl) concentration in phosphoric acidified medium pH 2.5 on removal of off-flavor from red radish anthocyanin. The effect of NaCl concentration on anthocyanin properties was also evaluated. Results showed that the total glucosinolate was highly degraded at high NaCl concentration (< 500 mM) compared with control, leading to higher off-flavor development. Additionally, the glucosinolate degradation was positively and significantly correlated to isothiocyanate, while was negatively and significantly correlated with dimethyl di-, trisulfide, cedrol, triacetin, 6-methyl-5-hepten-2-one. Moreover, total monomeric and color properties of extracted anthocyanins were degraded at high NaCl concentration (< 500 mM) compared with control. The tentative anthocyanin identification by UPLC-TQ-MS showed 12 glycosylated anthocyanins substituted at C3 and C5 in tested anthocyanin extracts. In conclusion, higher NaCl concentration (< 500 mM) could not be useful for red radish off-flavor removal and anthocyanin properties.

Characterization and sub-cellular localization of GalNAc-binding proteins isolated from human hepatic stellate cells.

Although the expression levels of total GalNAc-binding proteins (GNBPs) were up-regulated significantly in human hepatic stellate cells (HSCs) activated with transforming growth factor-ß1(TGF-ß1), yet little is known about the precise types, distribution and sub-cellular localization of the GNBPs in HSCs. Here, 264 GNBPs from the activated HSCs and 257 GNBPs from the quiescent HSCs were identified and annotated. A total of 46 GNBPs were estimated to be significantly up-regulated and 40 GNBPs were estimated to be significantly down-regulated in the activated HSCs. For example, the GNBPs (i.e. BTF3, COX17, and ATP5A1) responsible for the regulation of protein binding were up-regulated, and those (i.e. FAM114A1, ENO3, and TKT) responsible for the regulation of protein binding were down-regulated in the activated HSCs. The motifs of the isolated GNBPs showed that Proline residue had the maximum preference in consensus sequences. The western blotting showed the expression levels of COX17, and PRMT1 were significantly up-regulated, while, the expression level of CLIC1(B5) was down-regulated in the activated HSCs and liver cirrhosis tissues. Moreover, the GNBPs were sub-localized in the Golgi apparatus of HSCs. In conclusion, the precision alteration of the GNBPs referred to pathological changes in liver fibrosis/cirrhosis may provide useful information to find new molecular mechanism of HSC activation and discover the biomarkers for diagnosis of liver fibrosis/cirrhosis as well as development of new anti-fibrotic strategies.

N-Glycan Profiles of Neuraminidase from Avian Influenza Viruses.

The cleavage of sialic acids by neuraminidase (NA) facilitates the spread of influenza A virus (IV) descendants. Understanding the enzymatic activity of NA aids research into the transmission of IVs. An effective method for purifying NA was developed using p-aminophenyloxamic acid-modified functionalized hydroxylated magnetic particles (AAMPs), and from 0.299 to 0.401 mg of NA from eight IV strains was isolated by 1 mg AAMP. A combination of lectin microarrays and MALDI-TOF/TOF-MS was employed to investigate the N-glycans of isolated NAs. We found that more than 20 N-glycans were identified, and 16 glycan peaks were identical in the strains derived from chicken embryo cultivation. Multi-antennae, bisected, or core-fucosylated N-glycans are common in all the NAs. The terminal residues of N-glycans are predominantly composed of galactose and N-acetylglucosamine residues. Meanwhile, sialic acid residue was uncommon in these N-glycans. Further computational docking analysis predicted the interaction mechanism between NA and p-aminophenyloxamic acid.

Whole-exome sequencing in a cohort of Chinese patients with isolated cervical dystonia.

Background: Dystonia is a kind of movement disorder but its pathophysiological mechanisms are still largely unknown. Recent evidence reveals that genetical defects may play important roles in the pathogenesis of dystonia. Objectives and Methods: -To explore possible causative genes in Chinese dystonia patients, DNA samples from 42 sporadic patients with isolated cervical dystonia were subjected to whole-exome sequencing. Rare deleterious variants associated with dystonia phenotype were screened out and then classified according to the American College of Medical Genetics and Genomics (ACMG) criteria. Phenolyzer was used for analyzing the most probable candidates correlated with dystonia phenotype, and SWISS-MODEL server was for predicting the 3D structures of variant proteins. Results: Among 42 patients (17 male and 25 female) recruited, a total of 36 potentially deleterious variants of dystonia-associated genes were found in 30 patients (30/42, 71.4 %). Four disease-causing variants including a pathogenic variant in PLA2G6 (c.797G > C) and three likely pathogenic variants in DCTN1 (c.73C > T), SPR (c.1A > C) and TH (c.56C > G) were found in four patients separately. Other 32 variants were classified as uncertain significance in 26 patients. Phenolyzer prioritized genes TH, PLA2G6 and DCTN1 as the most probable candidates correlated with dystonia phenotype. Although 3D prediction of DCTN1 and PLA2G6 variant proteins detected no obvious structural alterations, the mutation in DCTN1 (c.73C > T:p.Arg25Trp) was closely adjacent to its key functional domain. Conclusion: Our whole-exome sequencing results identified a novel variant in DCTN1 in sporadic Chinese patients with isolated cervical dystonia, which however, needs our further study on its exact role in dystonia pathogenesis.

Age- and sex-associated differences in the glycopatterns of human salivary glycoproteins and their roles against influenza A virus.

Recent studies have elucidated that expression of certain glycoproteins in human saliva is increased or decreased according to age; meanwhile, human saliva may inhibit viral infection and prevent viral transmission. However, little is known about the age- and sex-associated differences in the glycopatterns of human salivary glycoproteins and their significant roles against influenza A virus (IVA). Here, we investigate the glycopatterns of human salivary glycoproteins with 180 healthy saliva samples divided into six age/sex groups using lectin microarrays and fabricate saliva microarrays to validate the terminal carbohydrate moieties of glycoproteins in individual saliva samples. Furthermore, we assess the inhibiting and neutralizing activity of saliva against two strains of influenza A (H9N2) virus. We find that seven lectins (e.g., MAL-II and SNA) show significant age differences in both females and males, and seven lectins (e.g., WFA and STL) show significant sex differences in children, adults and elderly people. Interestingly, we observe that elderly individuals have strongest resistance to IVA partly by presenting more terminal α2-3/6-linked sialic acid residues in their saliva, which bind with the influenza viral hemagglutinations. We conclude that age- and sex-associated differences in the glycopatterns of human salivary glycoproteins may provide pivotal information to help understand some age related diseases and physiological phenomena.

Influence of Pre-Heat Treatment on the Deformation Behaviors, Microstructural Characteristics, and Mechanical Properties of a Continuously Cast Al-Cu-Mg Alloy during Continuous Extrusion Process.

The presence of a second phase in Al-Cu-MG alloys, with various sizes and supersaturation-solid-solubility, which can be changed by pre-heat-treatment, could have remarkable influence on hot workability and mechanical performance. In the present work, a continuously cast 2024 Al alloy was homogenized and then subjected to hot compression and continuous extrusion (Conform) along with the initial as-cast alloy. The results showed that the 2024 Al alloy specimen with pre-heat treatment had a higher resistance to deformation and dynamic recovery (DRV) during hot compression process compared with the as-cast sample. Meanwhile, dynamic recrystallization (DRX) was advanced in the pre-heat-treated sample. After the Conform Process, the pre-heat-treated sample also attained better mechanical properties without additional solid solution treatment. The higher supersaturation solid solubility and dispersoids generated during pre-heat treatment was proved to play a key role in restricting boundary migration, tangling dislocation motion and promoting the precipitation of S phase, which raised resistance to DRV and plastic deformation and enhanced the mechanical properties.

Mutual regulation between glycosylation and transforming growth factor-ß isoforms signaling pathway.

Transforming growth factor-beta (TGF-ß) superfamily members orchestrate a wide breadth of biological processes. Through Sma and Mad (Smad)-related dependent or noncanonical pathways, TGF-ß members involve in the occurrence and development of many diseases such as cancers, fibrosis, autoimmune diseases, cardiovascular diseases and brain diseases. Glycosylation is one kind of the most common posttranslational modifications on proteins or lipids. Abnormal protein glycosylation can lead to protein malfunction and biological process disorder, thereby causing serious diseases. Previously, researchers commonly make comprehensive systematic overviews on the roles of TGF-ß signaling in a specific disease or biological process. In recent years, more and more evidences associate glycosylation modification with TGF-ß signaling pathway, and we can no longer disengage and ignore the roles of glycosylation from TGF-ß signaling to make investigation. In this review, we provide an overview of current findings involved in glycosylation within TGF-ßs and theirs receptors, and the interaction effects between glycosylation and TGF-ß subfamily signaling, concluding that there is an intricate mutual regulation between glycosylation and TGF-ß signaling, hoping to present the glycosylation regulatory patterns that concealed in TGF-ßs signaling pathways.

Characteristic Components and Authenticity Evaluation of Chinese Honeys from Three Different Botanical Sources.

We aimed to identify the characteristic phytochemicals of safflower, Chinese sumac, and bauhinia honeys to assess their authenticity. We discovered syringaldehyde, riboflavin, lumiflavin, lumichrome, rhusin [(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one-O-cinnamoyl oxime], bitterin {4-hydroxy-4-[3-(1-hydroxyethyl) oxiran-2-yl]-3,5,5-trimethylcyclohex-2-en-1-one}, and unedone as characteristic phytochemicals of these three types of honeys. The average contents of syringaldehyde, riboflavin, lumiflavin, or lumichrome in safflower honey were 41.20, 5.24, 24.72, and 36.72 mg/kg; lumiflavin, lumichrome, and rhusin in Chinese sumac honey were 39.66, 40.55, and 2.65 mg/kg; bitterin, unedone, and lumichrome in bauhinia honey were 8.42, 26.33, and 8.68 mg/kg, respectively. To our knowledge, the simultaneous presence of riboflavin, lumichrome, and lumiflavin in honey is a novel finding responsible for the bright-yellow color of honey. Also, it is the first time that lumiflavin, rhusin, and bitterin have been reported in honey. We effectively distinguish pure honeys from adulterations, based on characteristic components and high-performance liquid chromatography fingerprints; thus, we seem to provide intrinsic markers and reliable assessment criteria to assess honey authenticity.

Characterization of aberrant glycosylation associated with osteoarthritis based on integrated glycomics methods.

BACKGROUND: Osteoarthritis (OA) is the most common form of arthritis, affecting millions of aging people. Investigation of abnormal glycosylation is essential for the understanding of pathological mechanisms of OA. METHODS: The total protein was isolated from OA (n = 13) and control (n = 11) cartilages. Subsequently, glycosylation alterations of glycoproteins in OA cartilage were investigated by lectin microarrays and intact glycopeptides analysis. Finally, the expression of glycosyltransferases involved in the synthesis of altered glycosylation was assessed by qPCR and GEO database. RESULTS: Our findings revealed that several glycopatterns, such as α-1,3/6 fucosylation and high-mannose type of N-glycans were altered in OA cartilages. Notably, over 27% of identified glycopeptides (109 glycopeptides derived from 47 glycoproteins mainly located in the extracellular region) disappeared or decreased in OA cartilages, which is related to the cartilage matrix degradation. Interestingly, the microheterogeneity of N-glycans on fibronectin and aggrecan core protein was observed in OA cartilage. Our results combined with GEO data indicated that the pro-inflammatory cytokines altered the expression of glycosyltransferases (ALG3, ALG5, MGAT4C, and MGAT5) which may contribute to the alterations in glycosylation. CONCLUSION: Our study revealed the abnormal glycopatterns and heterogeneities of site-specific glycosylation associated with OA. To our knowledge, it is the first time that the heterogeneity of site-specific N-glycans was reported in OA cartilage. The results of gene expression analysis suggested that the expression of glycosyltransferases was impacted by pro-inflammatory cytokines, which may facilitate the degradation of protein and accelerate the process of OA. Our findings provide valuable information for the understanding of molecular mechanisms in the pathogenesis of OA.

Machine learning reveals salivary glycopatterns as potential biomarkers for the diagnosis and prognosis of papillary thyroid cancer.

The diagnosis of thyroid cancer, especially papillary thyroid cancer (PTC), is increasing rapidly worldwide. In this study, we aimed to study the glycosylation of salivary proteins associated with PTC and assess the likelihood that salivary glycopatterns may be a potential biomarker of PTC diagnosis. Firstly, 22 benign thyroid nodule (BTN) samples, 27 PTC samples, and 30 healthy volunteers (HV) samples were collected to probe the difference of salivary glycopatterns associated with PTC using lectin microarrays. Then, five machine learning models including K-Nearest Neighbor (KNN), Multilayer Perceptron (MLP), Logistic Regression (LR), Random Forest (RF), and Support Vector Machine (SVM) were established to distinguish HV, BTN and PTC based on the changes of salivary glycopatterns. As a result, SVM had the best diagnostic effect with an accuracy rate of 92 % in testing set. Besides, lectin microarrays were used to explore the differences in salivary glycopatterns of 26 paired salivary samples of PTC patients before and after operation in order to probe into salivary glycopatterns as potential biomarkers for prognosis of PTC patients. The results showed that the levels of salivary glycopatterns recognized by 6 different lectins in patients after the operation almost convergenced with HVs. This study could help to screen and assess patients with PTC and their prognosis based on precise changes of salivary glycopatterns.

Role of salivary glycopatterns for oral microbiota associated with gastric cancer.

Microbiota in the oral cavity plays an important role in maintaining human health. Our previous studies have revealed significant alterations of salivary glycopatterns in gastric cancer (GC) patients, but it is unclear whether these altered salivary glycopatterns can cause the dysbiosis of oral microbiota. In this study, the oral microbiome of healthy volunteers (HVs) and GC patients were detected. The neoglycoproteins were then synthesized according to the altered glycopatterns in GC patients and used to explore the effects of specific salivary glycopattern against oral microbiota. The results showed that five species were significantly increased (p < 0.05) while two species were significantly decreased (p < 0.01) in the saliva of GC patients compared with that of HVs. And the fucose-neoglycoproteins (30-100 µg/mL) could reduce the adhesion and toxicity of Aggregatibacter segnis (A. segnis) to oral cells (HOEC and CAL-27), change the glycan structures of lipopolysaccharide on the surface of A. segnis, and enhance the capacity of A. segnis to trigger innate immune responses. This study revealed that the changes of salivary protein glycopatterns in GC patients might contribute to the dysbiosis of oral microbiota, and had important implications in developing new carbohydrate drugs to maintain a balanced microbiota in the oral.

Elevation of α-1,3 fucosylation promotes the binding ability of TNFR1 to TNF-α and contributes to osteoarthritic cartilage destruction and apoptosis.

BACKGROUND: Osteoarthritis (OA) is the most common form of arthritis and is characterized by the degradation of articular cartilage and inflammation of the synovial membrane. Fucosylation is an important feature of protein N/O-glycosylation and is involved in a variety of pathological processes, including inflammation and cancer. However, whether fucosylation impacts the OA pathological process is unknown. METHODS: Total proteins were extracted from cartilage samples obtained from patients with OA (n = 11) and OA rabbit models at different time points (n = 12). OA-associated abnormal glycopatterns were evaluated by lectin microarrays and lectin blots. The expression of fucosyltransferases involved in the synthesis of α-1,3 fucosylation was assessed by semi-qPCR. The synthesis of α-1,3 fucosylation mediated by FUT10 was interrupted by the transfection of siRNA, and the effect of α-1,3 fucosylation on OA-associated events was assessed. Then, immunoprecipitation and lectin blotting were used to investigate the relationship between the α-1,3 fucosylation level of tumor necrosis factor receptor superfamily member 1A (TNFR1) and OA. Finally, a TNFR1 antibody microarray was fabricated to evaluate the effect of α-1,3 fucosylation on the ability of TNFR1 to bind to tumor necrosis factor-α (TNF-α). RESULTS: Elevated α-1,3 fucosylation was observed in cartilage from OA patients, rabbit models, and chondrocytes induced by TNF-α (fold change> 2, p< 0.01). Our results and the GEO database indicated that the overexpression of FUT10 contributed to this alteration. Silencing the expression of FUT10 impaired the ability of TNFR1 to bind to TNF-α, impeded activation of the NF-κB and P38/JNK-MAPK pathways, and eventually retarded extracellular matrix (ECM) degradation, senescence, and apoptosis in chondrocytes exposed to TNF-α. CONCLUSION: The elevation of α-1,3 fucosylation is not only a characteristic of OA but also impacts the OA pathological process. Our work provides a new positive feedback loop of "inflammation conditions/TNF-α/FUT10/α-1,3 fucosylation of TNFR1/NF-κB and P38/JNK-MAPK pathways/proinflammatory processes" that contributes to ECM degradation and chondrocyte apoptosis.

Bioinformatics analysis reveals that ANXA1 and SPINK5 are novel tumor suppressor genes in patients with oral squamous cell carcinoma.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is a solid tumor of squamous epithelial origin. Currently, surgery is still the main treatment for OSCC, with radiotherapy and chemotherapy as important adjuvant treatments. However, the problem of poor prognosis of OSCC patients still exists in clinical practice. To explore further potential biomarkers or treatment targets in OSCC patients, this study used a high-throughput gene expression database to study the potential molecular mechanisms of OSCC carcinogenesis. METHODS: The GEO database related to OSCC was searched and analyzed using GEO2R. Oncomine and the Human Protein Atlas were used to evaluate the expression level of differentially-expressed genes (DEGs). The cBioPortal dataset was used to analyze the mutations of the potential DEGs and patient survival. RESULTS: Three GEO datasets, GSE146483, GSE138206, and GSE148944, were downloaded and 7 DEGs were found in common in OSCC tissues. Using Oncomine and the Human Protein Atlas, ANXA1, IL1RN, and SPINK5 were decreased in cancer tissues, while protein levels of APOE and IFI35 were increased accordingly. Interestingly, low levels of ANXA1 and SPINKS were associated with the TNM stage of OSCC patients. No mutations in DEGs were found in OSCC patients, based on the cBioPortal dataset. Survival analysis indicated OSCC patients with high MSR1 had poor overall survival (OS), while low expression of CXCR4, ANXA1, IL1RN, and SPINK5 also predicted poor OS in OSCC patients. CONCLUSIONS: Our findings uncovered 7 potential biomarkers of OSCC patients, with ANXA1 and SPINK5 serving as potential tumor suppressor genes in OSCC.

Integrated glycomics strategy for the evaluation of glycosylation alterations in salivary proteins associated with type 2 diabetes mellitus.

Glycosylation is involved in several biological processes, and its alterations can reflect the process of certain diseases. Type 2 diabetes mellitus (T2DM) has attained the status of a global pandemic; however, the difference in salivary protein glycosylation between healthy subjects and patients with T2DM has not been fully understood. In the present study, salivary specimens from patients with T2DM (n = 72) and healthy volunteers (HVs, n = 80) were enrolled and divided into discovery and validation cohorts. A method combining the lectin microarray and lectin blotting was employed to investigate and confirm the altered glycopatterns in salivary glycoproteins. Then, lectin-mediated affinity capture of glycoproteins and MALDI-TOF/TOF-MS were performed to obtain the precise structural information of the altered glycans. As a result, the glycopatterns recognized by 5 lectins (LEL, VVA, Jacalin, RCA120 and DSA) showed significant alteration in the saliva of T2DM patients. Notably, the glycopattern of Galß-1,4GlcNAc (LacNAc) recognized by LEL exhibited a significant increase in T2DM patients compared to HVs in both discovery and validation cohorts. The MALDI-TOF/TOF-MS results indicated that there were 10 and 7 LacNAc-containing N/O-glycans (e.g. m/z 1647.586, 11 688.613 and 1562.470) that were identified only in T2DM patients. Besides, the relative abundance of 3 LacNAc-containing N-glycans and 10 LacNAc-containing O-glycans showed an increase in the glycopattern in T2DM patients. These results indicated that the glycopattern of LacNAc is increased in salivary glycoproteins from T2DM patients, and an increase in LacNAc-containing N/O-glycans may contribute to this alteration. Our findings provide useful information to understand the complex physiological changes in the T2DM patients.

Regulation of N6-Methyladenosine in the Differentiation of Cancer Stem Cells and Their Fate.

N6-methyladenosine (m6A) is one of the most common internal RNA modifications in eukaryotes. It is a dynamic and reversible process that requires an orchestrated participation of methyltransferase, demethylase, and methylated binding protein. m6A modification can affect RNA degradation, translation, and microRNA processing. m6A plays an important role in the regulation of various processes in living organisms. In addition to being involved in normal physiological processes such as sperm development, immunity, fat differentiation, cell development, and differentiation, it is also involved in tumor progression and stem cell differentiation. Curiously enough, cancer stem cells, a rare group of cells present in malignant tumors, retain the characteristics of stem cells and play an important role in the survival, proliferation, metastasis, and recurrence of cancers. Recently, studies demonstrated that m6A participates in the self-renewal and pluripotent regulation of these stem cells. However, considering that multiple targets of m6A are involved in different physiological processes, the exact role of m6A in cancer progression remains controversial. This article focuses on the mechanism of m6A and its effects on the differentiation of cancer stem cells, to provide a basis for elucidating the tumorigenesis mechanisms and exploring new potential therapeutic approaches.

The Tumor Suppressive Roles and Prognostic Values of STEAP Family Members in Breast Cancer.

OBJECTIVE: To investigate the expression patterns and prognostic values of STEAP family members in the occurrence and development of breast cancer. MATERIALS AND METHODS: The Human Protein Atlas was used to analyze the expression level of STEAPs in human normal tissues and malignant tumors. ONCOMINE datasets were analyzed for the comparison of the STEAPs levels between malignant cancers and corresponding normal tissues. Kaplan-Meier plotter was used to analyze the prognostic value of STEAPs in breast cancer patients. RESULTS: STEAPs were widely distributed in human normal tissues with diverse levels. Normally, it is predicted that STEAP1 and STEAP2 were involved in the mineral absorption process, while STEAP3 participated in the TP53 signaling pathway and iron apoptosis. The results from ONCOMINE showed downregulation of STEAP1, STEAP2, and STEAP4 in breast cancers. Survival analysis revealed that breast cancer patients with high levels of STEAP1, STEAP2, and STEAP4 had a good prognosis, while those with low expression had high overall mortality. CONCLUSION: STEAP1, STEAP2, and STEAP4 are predicted to be the potential prognostic biomarkers for breast cancer patients, providing novel therapeutic strategies for them.