DNA-Encoded and Spatial Proximity Replaced Glycoprotein Analysis Reveals Glycosylation Heterogeneity of Extracellular Vesicles.

Glycosylation of proteins is an essential feature of extracellular vesicles (EVs). However, while the glycosylation heterogeneity focusing on specific EV subtypes and proteins will better reveal the functions of EVs, the determination of their specific glycans remains highly challenging. Herein, we report a method of protein-specific glycan recognition using DNA-encoded affinity ligands to label proteins and glycans. Manipulating the sequences of DNA tags and employing a DNA logic gate to trigger a spatial proximity-induced DNA replacement reaction enabled the release of glycan-representative DNA strands for the quantitative detection of multiple glycoforms. After size-dependent isolation of EV subgroups and decoding of three typical glycoforms on the epithelial growth factor receptor (EGFR), we found that the different EV subgroups of the EGFR glycoprotein varied with respect to glycan types and abundance. The distinctive glycoforms of the EV subgroups could interfere with the EGFR-related EV functions. Furthermore, the sialylation of small EVs possessed the potential as a cancer biomarker. This method provides new insights into the role of protein-specific glycoforms in EV functions.

HnRNPAB promotes pancreatic ductal adenocarcinoma extravasation and liver metastasis by stablizing MYC mRNA.

Heterogeneous nuclear ribonucleoprotein AB (hnRNPAB) is considered a cancer-promoting heterogeneous nuclear ribonucleoprotein in many cancers, but its function in pancreatic ductal adenocarcinoma (PDAC) is poorly understood. HnRNPAB was highly expressed in PDAC tissues compared to normal pancreatic tissues, and high expression of hnRNPAB was associated with poor overall survival and recurrence-free survival in PDAC patients. HnRNPAB promotes migration and invasion of PDAC cells in vitro. In xenograft tumor mouse models, hnRNPAB deprivation significantly attenuated liver metastasis. HnRNPAB mRNA and protein levels are positively associated with MYC in PDAC cells. Mechanistically, hnRNPAB bound to MYC mRNA and prolonged its half-life of MYC mRNA. HnRNPAB induced PDAC cells to secret CXCL8 via MYC, which promoted neutrophils recruitment and facilitated tumor cells entrancing into the hepatic parenchyma. These findings point to a novel regulatory mechanism via which hnRNPAB promotes PDAC metastasis. Implications: Hnrnpab participates in the post-transcriptional regulation of the oncogene MYC by binding and stabilizing MYC mRNA, thereby promoting liver metastasis in PDAC.

Identification and validation of a ferroptosis-related gene signature for predicting survival in skin cutaneous melanoma.

PURPOSE: Ferroptosis plays a crucial role in the initiation and progression of melanoma. This study developed a robust signature with ferroptosis-related genes (FRGs) and assessed the ability of this signature to predict OS in patients with skin cutaneous melanoma (SKCM). METHODS: RNA-sequencing data and clinical information of melanoma patients were extracted from TCGA, GEO, and GTEx. Univariate, multivariate, and LASSO regression analyses were conducted to identify the gene signature. A 10 FRG signature was an independent and strong predictor of survival. The predictive performance was assessed using ROC curve. The functions of this gene signature were assessed by GO and KEGG analysis. The statuses of low-risk and high-risk groups according to the gene signature were compared by GSEA. In addition, we investigated the possible relationship of FRGs with immunotherapy efficacy. RESULTS: A prognostic signature with 10 FRGs (CYBB, IFNG, FBXW7, ARNTL, PROM2, GPX2, JDP2, SLC7A5, TUBE1, and HAMP) was identified by Cox regression analysis. This signature had a higher prediction efficiency than clinicopathological features (AUC = 0.70). The enrichment analyses of DEGs indicated that ferroptosis-related immune pathways were largely enriched. Furthermore, GSEA showed that ferroptosis was associated with immunosuppression in the high-risk group. Finally, immune checkpoints such as PDCD-1 (PD-1), CTLA4, CD274 (PD-L1), and LAG3 were also differential expression in two risk groups. CONCLUSIONS: The 10 FRGs signature were a strong predictor of OS in SKCM and could be used to predict therapeutic targets for melanoma.

Development and validation of a ferroptosis-related lncRNAs signature to predict prognosis and microenvironment for melanoma.

Ferroptosis plays an important role in cancer. However, studies about ferroptosis-related lncRNAs (FRLs) in skin cutaneous melanoma (SKCM) are scarce. Moreover, the relationship between prognostic FRLs and tumor microenvironment (TME) in melanoma remains unclear. This study investigates the potential prognostic value of FRLs and their association with TME in SKCM. The RNA-sequencing data of SKCM were downloaded from The Cancer Genome Atlas (TCGA) database. Melanoma patients were randomly divided into training and testing groups in a 1:1 ratio. A signature composed of 19 FRLs was developed by the least absolute shrinkage and selection operator (LASSO) regression analysis to divide patients into a low-risk group with a better prognosis and a high-risk group with a poor prognosis. Multivariate Cox regression analysis suggested that the risk score was an independent prognostic factor. The Area Under Curve (AUC) value of the risk score reached 0.768 in the training group and 0.770 in the testing group. Subsequent analysis proved that immune-related signaling pathways were significantly enriched in the low-risk group. The tumor immune cell infiltration analysis demonstrated that melanoma in the high-risk group tended to be immunologically "cold". We identified a novel FRLs signature which could accurately predict the prognosis of patients with melanoma.

Identification and Validation of Immune-Related lncRNA Signature as a Prognostic Model for Skin Cutaneous Melanoma.

PURPOSE: Skin cutaneous melanoma (SKCM) is the most aggressive skin cancer that results in high morbidity and mortality rate worldwide. Immune-related long non-coding RNAs (IRlncRs) play an important role in regulating gene expression in tumors. Therefore, in this study, we aimed to identify IRlncRs signature that could predict prognosis and therapeutic targets for melanoma irrespective of the gene expression levels. METHODS: RNA-sequencing data were obtained from The Cancer Genome Atlas (TCGA). IRlncRs were identified using co-expression analysis and recognized using univariate analysis. The impact of IRlncRs on survival was analyzed using a modified least absolute shrinkage and selection operator (Lasso) regression model. A 1-year survival receiver operating characteristic curve was constructed, and the area under the curve was calculated to identify the optimal cut-off point to distinguish between high and low-risk groups in patients with SKCM. Furthermore, integrative analysis was performed to identify the impact of clinicopathological features, chemotherapeutic treatment, tumor-infiltrating immune cells, and mutant genes on survival. RESULTS: A total of 28 IRlncRs significantly associated with survival were identified. Seventeen IRlncRs pairs were used to build a survival risk model that could be used to distinguish between low and high-risk groups. The high-risk group was negatively associated with tumor-infiltrating immune cells and had a higher half inhibitory centration for chemotherapeutic agents such as cisplatin and vinblastine. Additionally, the high-risk group had a positive correlation with the expression of specific mutant genes such as BRAF and KIT. CONCLUSION: Our findings demonstrate that some IRlncRs have a significant correlation with survival and therapeutic targets for SKCM patients and may provide new insight into the clinical diagnosis and treatment strategies for SKCM patients.

Mesenchymal stem cell-derived exosomes: therapeutic implications for rotator cuff injury.

Rotator cuff injuries are a common clinical condition of the shoulder joint. Surgery that involves reattaching the torn tendon to its humeral head bony attachment has a somewhat lower success rate. The scar tissue formed during healing of the rotator cuff leads to poor tendon-related mechanical properties. To promote healing, a range of genetic interventions, as well as cell transplantation, and many other techniques have been explored. In recent years, the therapeutic promise of mesenchymal stem cells (MSCs) has been well documented in animal and clinical studies. Some data have suggested that MSCs can promote angiogenesis, reduce inflammation and cell proliferation and increase collagen deposition. These functions are likely paracrine effects of MSCs, particularly mediated through exosomes. Here, we review the use of MSCs-related exosomes in tissues and organs. We also discuss their potential utility for treating rotator cuff injuries, and explore the underlying mechanisms of their effects.

Development and Validation of an Immune-Related Gene Pairs Signature in Grade II/III Glioma.

BACKGROUND: Gliomas are prevalent primary intracerebral malignant tumors. Increasing evidence indicates an association between the immune signature and Grade II/III glioma prognosis. Thus, we aimed to develop an immune-related gene pair (IRGP) signature that can be used as a prognostic tool in Grade II/III glioma. METHODS: The gene expression levels and clinical information of Grade II/III glioma patients were collected from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases. The TCGA data were randomly divided into a training cohort (n = 249) and a validation cohort (n = 162), and a CGGA dataset served as an external validation group (n = 605). IRGPs significantly associated with prognosis were selected by Cox regression. Gene set enrichment analysis and filtration were performed with the IRGPs. RESULTS: Within a set of 1991 immune genes, 8 IRGPs including 15 unique genes that significantly affect survival constituted a gene signature. In the validation datasets, the IRGP signature significantly stratified patients with Grade II/III glioma into low- and high-risk groups (P < 0.001), and the IRGP index was found to be an independent prognostic factor through univariate and multivariate analyses (P < 0.05). Additionally, 26 functional pathways were identified through the intersection of Gene Set Enrichment Analysis (GSEA) and Gene Ontology (GO) enrichment analysis. CONCLUSION: The IRGP signature demonstrated good prognostic value for Grade II/III gliomas, which may provide new insights into individual treatment for glioma patients. The IRGPs might function through the identified 26 functional pathways.

Non-Coding RNAs in Gastric Cancer: From Malignant Hallmarks to Clinical Applications.

Gastric cancer (GC) is one of the most lethal malignancies worldwide. However, the molecular mechanisms underlying gastric carcinogenesis remain largely unknown. Over the past decades, advances in RNA-sequencing techniques have greatly facilitated the identification of various non-coding RNAs (ncRNAs) in cancer cells, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs). Accumulating evidence has revealed that ncRNAs are essential regulators in GC occurrence and development. However, ncRNAs represent an emerging field of cancer research, and their complex functionality remains to be clarified. Considering the lack of viable biomarkers and therapeutic targets in GC, further studies should focus on elucidating the intricate relationships between ncRNAs and GC, which can be translated into clinical practice. In this review, we summarize recent research progress on how ncRNAs modulate the malignant hallmarks of GC, especially in tumor immune escape, drug resistance, and stemness. We also discuss the promising applications of ncRNAs as diagnostic biomarkers and therapeutic targets in GC, aiming to validate their practical value for clinical treatment.

Phytolith data in peat profile over the past 1300 years in the Xishan Mountains, Jiangxi Province, China.

Phytoliths are microscopic siliceous particles formed in the plants and preserved in the sediments after the plant death and decay. Phytolith formation is controlled by the plant genes and growing environments. As such, phytolith assemblages have been widely used in ancient plant composition analysis, paleoclimate reconstruction, and paleoenvironment reconstruction. For the effective utilization, phytolith description, nomenclature and classification are the most important. This article presents detailed original phytolith data from a peat profile (28°44'55.33″N, 115°39'59.80″N), which is related to the research article of "Climatic controls on peat swamp formation and evolution since 1300 year BP as recorded by phytoliths in the Xishan Mountains, Jiangxi Province, China" [1]. After extracted from peat, the phytoliths were observed under 400 × light microscope, described and nominated according to ICPN1.0 [2], and classified and counted more than 400 particles for each peat sample. 314 microscopic slides were observed and fifty types of phytolith were classified for the peat profile, including woody phytoliths, shrub phytoliths, herbaceous phytoliths and other unidentified morph types. All these provide basic information for paleo-researches.