A novel long non-coding RNA LINC00524 facilitates invasion and metastasis through interaction with TDP43 in breast cancer.

Breast cancer (BC) remains a significant health concern worldwide, with metastasis being a primary contributor to patient mortality. While advances in understanding the disease's progression continue, the underlying mechanisms, particularly the roles of long non-coding RNAs (lncRNAs), are not fully deciphered. In this study, we examined the influence of the lncRNA LINC00524 on BC invasion and metastasis. Through meticulous analyses of TCGA and GEO data sets, we observed a conspicuous elevation of LINC00524 expression in BC tissues. This increased expression correlated strongly with a poorer prognosis for BC patients. A detailed Gene Ontology analysis suggested that LINC00524 likely exerts its effects through RNA-binding proteins (RBPs) mechanisms. Experimentally, LINC00524 was demonstrated to amplify BC cell migration, invasion and proliferation in vitro. Additionally, in vivo tests showed its potent role in promoting BC cell growth and metastasis. A pivotal discovery was LINC00524's interaction with TDP43, which leads to the stabilization of TDP43 protein expression, an element associated with unfavourable BC outcomes. In essence, our comprehensive study illuminates how LINC00524 accelerates BC invasion and metastasis by binding to TDP43, presenting potential avenues for therapeutic interventions.

miR-107 is involved in the regulation of NEDD9-mediated invasion and metastasis in breast cancer.

BACKGROUND: As a metastasis-related protein, NEDD9 has been reported in breast cancer (BC) metastasis research. However, there are few studies on the upstream regulators of NEDD9, especially involving the potential role of miRNAs. The purpose of this study was to explain whether miR-107 potentially regulates NEDD9, which may lead to invasion and metastasis of BC. METHODS: MCF-7 and MDA-MB-231 cells were transduced with lentiviruses to construct stably transduced cells with miR-107 overexpression, miR-107 silencing or empty vectors. A luciferase reporter assay was performed to verify the binding of miR-107 and NEDD9. The scratch test and Transwell assay were used to measure cell migration and invasion ability, respectively. For the study of metastasis in vivo, we injected MDA-MB-231 cells into the fat pad of nude mice to develop an orthotopic breast cancer model. RESULTS: We found that NEDD9 expression correlates with the prognosis of BC patients. In BC cell lines, NEDD9 was positively correlated with cell migration ability. Further research revealed that miR-107 inhibited NEDD9 expression by targeting the 3'-untranslated region of NEDD9. Overexpression of miR-107 suppressed the expression of NEDD9, thereby inhibiting the invasion, migration and proliferation of BC cells, but interference with miR-107 promoted the expression of NEDD9 as well as invasion, migration and proliferation. In an in vivo model, overexpression of miR-107 decreased the expression of NEDD9 and inhibited tumour growth, invasion and metastasis; however, these effects were reversed by inhibiting miR-107. CONCLUSIONS: These findings indicated the potential role of miR-107 in regulating NEDD9 in the invasion, migration and proliferation of BC.

Inhibition of Musashi-1 enhances chemotherapeutic sensitivity in gastric cancer patient-derived xenografts.

Musashi-1 (MSI1), a neural RNA-binding protein, is considered a gastric and intestinal stem cell marker. Although the function of MSI1 in gastric cancer has attracted increasing interest, it is not known whether MSI1 can be used as a biomarker to monitor gastric cancer development and response to treatment. Here, the role of MSI1 in the chemotherapeutic sensitivity of gastric cancer was investigated. Patients with high MSI1 levels had poor outcomes, implicating the gene in the development and progression of the disease. We overexpressed and silenced MSI1 in the human gastric cancer cell lines MKN45 and HGC27, finding that knockdown reduced proliferation, invasion, and migration, while promoting apoptosis. A patient-derived xenograft gastric cancer model was constructed in which mice received chemical drugs, si-MSI1, or a drug-si-MSI1 combination. It was found that blocking MSI1 expression reduced gastric cancer drug tolerance. The combination treatment with si-MSI1 was superior to 5F-dUMP and cisplatin, either separately or in combination, indicating that including si-MSI1 was better than drug therapy alone. Transcriptome sequencing analysis showed that MSI1 altered cell cycle regulation and growth signal transduction, including that of blood vessel epicardial substance (BVES). These results suggest that MSI1 reduces the tolerance of gastric cancer to chemical drugs through modulation of MSI1/BVES signaling.

Mechanism of Synergistic Effect on Electron Transfer over Co-Ce/MCM-48 during Ozonation of Pharmaceuticals in Water.

The same amount of metal was deposited on the surface of three-dimensional mesoporous MCM-48 by a facile impregnation-calcination method for catalytic ozonation of pharmaceutical and personal-care products in the liquid phase. At 120 min reaction time, Co/MCM-48 and Ce/MCM-48 showed 46.6 and 63.8% mineralization for clofibric acid (CA) degradation, respectively. Less than 33% mineralization was achieved with Co/MCM-48 and Ce/MCM-48 during sulfamethazine (SMZ) ozonation. In the presence of monometallic oxides modified MCM-48 catalysts, total organic carbon (TOC) removal of diclofenac sodium (DCF) was around 80%. The composite Co-Ce/MCM-48 catalyst exhibited significantly higher activity in terms of TOC removal of CA (83.6%), SMZ (51.7%) and DCF (86.8%). Co-Ce/MCM-48 inhibited efficiently the accumulation of small molecular carboxyl acids during ozonation. A detailed research was conducted to detect the nature of material structure and mechanism of catalytic ozonation by using a series of characterizations. The main reaction pathway of CA was determined by the analysis of liquid chromatography-mass spectrometry, in line with the results of frontier electron density calculations that reactive oxygen species (ROSs) were easy to attack negative regions of pharmaceuticals. The Si-O-Si, Co···HO-Si-O-Si-OH···Ce, and O3···Co-HO-Si-O-Si-OH···Ce-OH···O3 basic units in catalysts were constructed to detect the orbit-energy-level difference. The results revealed that a synergistic effect existed at the interface between cobalt and cerium oxides over MCM-48, which facilitated the ROSs sequence in solution with ozone. Therefore, the multivalence redox coupling of Ce4+/Ce3+ and Co3+/Co2+ along with electron transfer played an important role in catalytic ozonation process.