An intratumor bacteria-targeted DNA nanocarrier for multifaceted tumor microenvironment intervention.

Intratumor bacteria, which are involved with complex tumor development mechanisms, can compromise the therapeutic efficiencies of cancer chemotherapeutics. Therefore, the development of anti-tumor agents targeting intratumor bacteria is crucial in overcoming the drug inactivation induced by bacteria colonization. In this study, a double-bundle DNA tetrahedron-based nanocarrier is developed for intratumor bacteria-targeted berberine (Ber) delivery. The combination of aptamer modification and high drug loading efficacy endow the DNA nanocarrier TA@B with enhanced delivery performance in anti-tumor therapy without obvious systemic toxicity. The loaded natural isoquinoline alkaloid Ber exhibits enhanced antimicrobial, anticancer, and immune microenvironment regulation effects, ultimately leading to efficient inhibition of tumor proliferation. This intratumor bacteria-targeted DNA nanoplatform provides a promising strategy in intervening the bacteria-related microenvironment and facilitating tumor therapy.

FAM46A expression is elevated in glioblastoma and predicts poor prognosis of patients.

OBJECTIVE: To study the expression of FAM46A in glioblastoma (GBM) and analyze its significance in predicting the prognosis of patients. MATERIALS AND METHODS: mRNA expression and clinical data of patients with GBM were retrieved from ONCOMINE databases and The Cancer Genome Atlas (TCGA) database. Immunohistochemistry was performed in a tissue microarray including 110 GBM cases and 12 normal controls to determine the expression of FAM46A protein. Then, Kaplan-Meier curve and Cox regression model were used to investigate the relationship between FAM46A expression and clinical outcome. Coexpressed genes of FAM46A were analyzed by Linked Omics, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). RESULTS: Upregulated expression of FAM46A was found in both TCGA and our cohort. High FAM46A expression was associated with the poor prognosis of patients with GBM and could be identified as an independent risk factor for overall survival (HR = 1.652, p = 0.022). Further bioinformatics analysis revealed that FAM46A might be involved in cell motility and endoplasmic reticulum proteostasis and stress to promote GBM progression. CONCLUSION: Our findings suggest that increased expression of FAM46A in GBM is a novel biomarker for predicting poor outcome of patients and that targeting FAM46A may serve as a potential therapy for this disease.

SNHG1 Promotes Malignant Progression of Glioma by Targeting miR-140-5p and Regulating PI3K/AKT Pathway.

PURPOSE: To explore the regulatory mechanism of long non-coding RNA small nucleolar RNA host gene 1 (SNHG1) in glioma. MATERIALS AND METHODS: The expression of SNHG1 and miR-140-5p in glioma tissues and glioma cell lines (LN-18, KNS-81, and KALS-1) was determined, and the effect of the two on cell proliferation, invasion, and PI3K/AKT pathway was analyzed. RESULTS: SNHG1 was overexpressed in glioma tissues, while miR-140-5p was underexpressed in them, and there was a significant negative correlation between SNHG1 and miR-140-5p. In addition, both down-regulation of SNHG1 and up-regulation of miR-140-5p significantly inhibited the malignant proliferation and invasion of glioma, intensified the apoptosis, and also significantly suppressed the activation of the PI3K/AKT pathway. The dual-luciferase reporter assay, RNA pull-down assay, and RIP determination all confirmed that there was a targeting relationship between SNHG1 and miR-140-5p, and there was no difference between KNS-81 and KALS-1 cells transfected with SNHG1+mimics and si-SNHG1+inhibitor and those in the si-NC group with unrelated sequences in terms of cell malignant progression. CONCLUSION: SNHG1/miR-140-5p axis and its regulation on PI3K/AKT pathway might be a novel therapeutic direction to curb the malignant progression of glioma.

SLC34A2 promotes neuroblastoma cell stemness via enhancement of miR-25/Gsk3ß-mediated activation of Wnt/ß-catenin signaling.

Cancer stem cells contribute to cancer progression, but the mechanisms underlying neuroblastoma stem cell development are unclear. Here, we examined the roles of the transcription factor SLC34A2 in regulating the stemness of neuroblastoma cells. We found that SLC34A2 expression was negatively correlated with the overall survival and relapse-free survival probability of neuroblastoma patients. Additionally, SLC34A2 expression was observed to be remarkably increased in spheroids derived from neuroblastoma cells. Knockdown of SLC34A2 attenuated the expression of stemness markers and spheroid formation capacity of neuroblastoma cell-derived spheroids, and overexpression of SLC34A2 exerted the opposite effects in neuroblastoma cells. Mechanistically, SLC34A2 was found to directly bind to the promoter of MIR25, which targets glycogen synthesis kinase 3ß (Gsk3ß), an antagonist of Wnt signaling. Transfection of miR-25 inhibitor or a Gsk3ß overexpression plasmid attenuated the effects of SLC34A2 overexpression on the stemness of neuroblastoma cells. Our results demonstrate that miR-25/Gsk3ß-mediated activation of Wnt signaling is responsible for SLC34A2-induced enhancement of neuroblastoma cell stemness.