Minimally invasive surgical approach versus open procedure for pancreaticoduodenectomy: A systematic review and meta-analysis

An update on the role of miR-124 in the pathogenesis of human disorders

Abstract Background: The mesenchymal stem cells (MSCs) have enormous therapeutic potential owing to their multi-lineage differentiation and self-renewal properties. MSCs express growth factors, cytokines, chemokines, and non-coding regulatory RNAs with immunosuppressive, anti-tumor, and migratory properties. MSCs also release several anti-cancer molecules via extracellular vesicles, that act as pro-apoptotic/tumor suppressor factors. This study aimed to identify the stem cell-derived secretome that could exhibit anti-cancer properties through molecular profiling of cargos in MSC-derived exosomes. Methods: Human umbilical cord mesenchymal stem cells (hUCMSCs) were isolated from umbilical cord tissues and culture expanded. Subsequently, exosomes were isolated from hUCMSC conditioned medium and characterized by DLS, electron microscopy. Western blot for exosome surface marker protein CD63 expression was performed. The miRNA profiling of hUCMSCs and hUCMSC-derived exosomes was performed, followed by functional enrichment analysis. Results: The tri-lineage differentiation potential, fibroblastic morphology, and strong expression of pluripotency genes indicated that isolated fibroblasts are MSCs. The isolated extracellular vesicles were 133.8 ± 42.49 nm in diameter, monodispersed, and strongly expressed the exosome surface marker protein CD63. The miRNA expression profile and gene ontology (GO) depicted the differential expression patterns of high and less-expressed miRNAs that are crucial to be involved in the regulation of apoptosis. The LCMS/MS data and GO analysis indicate that hUCMSC secretomes are involved in several oncogenic and inflammatory signaling cascades. Conclusion: Primary human MSCs released miRNAs and growth factors via exosomes that are increasingly implicated in intercellular communications, and hUCMSC-exosomal miRNAs have a critical influence in regulating cell death and apoptosis of cancer cells. Graphical abstract 

/pdf/a-comprehensive-cancer-associated-microrna-expression-3cxn43nc.pdf

A Comprehensive Cancer-Associated MicroRNA Expression Profiling and Proteomic Analysis of Human Umbilical Cord Mesenchymal Stem Cell-Derived Exosomes

Abnormal circular RNA (circRNA) expression correlates with human traits such as many kinds of cancers. Though circRNAs have links to cancer, they have less characterization in metastatic castration-resistant prostate cancer (PCa), which is main reason for PCa mortality. Therefore, high-throughput sequencing was used for selected circRNA profiles. The result showed that circ-TRPS1 was upregulated significantly in high-grade PCa tissues or cell lines. High circ-TRPS1 expression correlated to aggressive PCa phenotypes. Knockdown of circ-TRPS1 suppressed PCa proliferation and metastasis through targeting miR-124-3p/EZH2 axis-mediated stemness in PCa, which was validated by luciferase reporter assays. EZH2 overexpression or miR-124-3p inhibition reversed the inhibition of circ-TRPS1 silencing in PCa cell migration and proliferation by recovering stemness. In summary, data demonstrated that circ-TRPS1 suppressed PCa progression through functioning similar to a miR-124-3p sponge to enhance EZH2 expression and cancer stem-like cell differentiation. Thus, circ-TRPS1 might be a candidate target for PCa treatment.

Downregulation of circ-TRPS1 suppressed prostatic cancer prognoses by regulating miR-124-3p/EZH2 axis-mediated stemness.

Abstract Background As a skeletal malignancy, osteosarcoma has high incidence among primary malignant bone tumors. With increasing researches on molecules which mediate cancer progression, molecular mechanism has gradually become the pivot of osteosarcoma research and treatment. Aim Our study aimed at investigating the function of G3BP stress granule assembly factor 2 (G3BP2), which is an oncogene for breast cancer (BC) and prostate cancer but remains unknown in osteosarcoma cells. Methods Related gene expression was confirmed by RT-qPCR. Functional assays including immunofluorescence (IF), colony formation, transferase-mediated dUTP nick-end labeling (TUNEL) as well as transwell assays were utilized to test the cell biological process caused by the genes. Meanwhile, RNA pull-down assay, along with luciferase reporter and RNA immunoprecipitation (RIP) assays, was utilized to detect the interaction G3BP2, miR-124-3p and FGD5 antisense RNA 1 (FGD5-AS1) may exert on the regulation of osteosarcoma cells. Results G3BP2 was with high expression in osteosarcoma cells, and it aggravated the malignant cell behaviors in osteosarcoma. Additionally, miR-124-3p was verified to negatively regulate G3BP2 expression in osteosarcoma cells. Moreover, lncRNA FGD5-AS1 was predicted and testified to be the sponge of miR-124-3p and modulated G3BP2 expression positively. Subsequently, FGA5-AS1 accelerated osteosarcoma cell proliferation through up-regulating G3BP2. Furthermore, we identified EBF transcription factor 1 (EBF1) as the transcription factor for FGA5-AS1, and EBF1 served as a tumor facilitator in osteosarcoma cells. Conclusion EBF1 induced-FGA5-AS1 aggravated osteosarcoma cell malignancy by targeting miR-124-3p and G3BP2. 

https://josr-online.biomedcentral.com/counter/pdf/10.1186/s13018-022-03181-7

EBF1-mediated up-regulation of lncRNA FGD5-AS1 facilitates osteosarcoma progression by regulating miR-124-3p/G3BP2 axis as a ceRNA

Activity and safety of preclinical and a phase 1 study of purinostat mesylate, a uniquely potent and selective hdac i/iib inhibitor in relapsed or refractory lymphoma

Preclinical and a phase 1 study of purinostat mesylate, a novel hdac i/iib selective inhibitor, for the treatment of relapsed or refractory multiple myeloma

BACKGROUND Tuberculosis remains a global public health problem. Genetic polymorphisms may affect the susceptibility, clinical characteristics, and adverse drug reactions of patients with TB. The present study aimed to examine the association of single nucleotide polymorphisms of lncRNA-HNF1B-3:1 with the clinical manifestation of TB in a Western Chinese population. METHOD A total of 526 tuberculosis patients and 561 healthy subjects were recruited in Western China. The correlation between lnc-HNF1B-3:1 polymorphism and tuberculosis susceptibility was investigated. Moreover, the influence on adverse drug reactions following treatment was explored. A total of 7 SNPs within the lnc-HNF1B-3:1 locus was genotyped by the improved multiplex ligation detection reaction method. RESULTS No significant associations were noted between TB susceptibility and the presence of all 7 SNPs of the lnc-HNF1B-3:1 as determined by single-locus analysis (All P > .05). The AA genotype of rs12939622 (in the dominant model) and the AA genotype of rs4262994 (in the recessive model) caused increased susceptibility of the subjects to fever (P < .001 and P = .008, respectively). The Rs2542670 G allele was associated with increased risk of thrombocytopenia, leukopenia, and chronic kidney damage following drug administration (P = .007, .029, .003, respectively). CONCLUSION The present study reported for the first time that the rs12939622, rs4262994 and rs2542670 genotypes in lnc-HNF1B-3:1 locus may influence the clinical manifestations of tuberculosis.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/jcla.23076

Clinical relevance of the lnc-HNF1B-3:1 genetic polymorphisms in Western Chinese tuberculosis patients.

BACKGROUND Gastric cancer is one of the major malignant tumors in the world. Integrins expressed in cancer cells can promote tumor progression and migration. MiRNAs can inhibit the expression of target genes by directly binding to their mRNAs and can affect various important biological processes. The aim of this study was to investigate the role of miR-124- 3p and ITGB3 in gastric cancer. METHODS RT-PCR and western blot are used to detect the expression of miR-124-3p, ITGB3 and integrin β3 in gastric cancer tissues and cells. The wound healing, CCK-8 assay, transwell migration and invasion assay were performed to determine the cell proliferation, migration and invasion. What’s more, bioinformatics prediction and luciferase assay was conducted to demonstrated the binding efficiency between miR-124-3p and ITGB3. RESULTS We verified that ITGB3 and miR-124-3p changes the migration and invasion of gastric cancer cells in vitro. The overexpression or silencing of miR-124-3p inhibited or promoted the proliferation, migration and invasion of both selected gastric cancer cells, and ITGB3 is just the reverse. Meanwhile, we validated that ITGB3 is the target of miR-124-3p by bioinformatics prediction and luciferase assay. Lastly, the expression of ITGB3 in 40 pairs of gastric cancer tissues were significantly higher than that in the adjacent normal tissues, while the expression level of miR-124-3p was significantly decreased in cancer tissues. CONCLUSIONS miR-124-3p inhibits the migration and invasion of Gastric cancer by targeting ITGB3 in gastric cancer cells. Our results suggested that miR-124-3p and ITGB3 may reasonably serve as a promising therapeutic target.

MiR-124-3p inhibits the migration and invasion of Gastric cancer by targeting ITGB3.

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Activity and safety of preclinical and a phase 1 study of purinostat mesylate, a uniquely potent and selective hdac i/iib inhibitor in relapsed or refractory lymphoma

Preclinical and a phase 1 study of purinostat mesylate, a novel hdac i/iib selective inhibitor, for the treatment of relapsed or refractory multiple myeloma

Clinical relevance of the lnc-HNF1B-3:1 genetic polymorphisms in Western Chinese tuberculosis patients.

MiR-124-3p inhibits the migration and invasion of Gastric cancer by targeting ITGB3.