Breast cancer (BC) is the most frequently diagnosed cancer and the leading cause of cancer-related death among women worldwide. Evidence indicates that posttranscriptional N6-methyladenosine (m6A) modification modulates BC development. In the present study, we assessed BC and normal tissues to investigate this connection. RNA m6A levels were determined by methylation quantification assay. The effects of methyltransferase-like 14 (METTL14) gain-of-expression or co-transfection with an m6A inhibitor on cell migration and invasion abilities were determined by Transwell assays. The levels of differentially expressed (DE) miRNAs were verified by real-time quantitative PCR (RT-qPCR). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes analyses (KEGG) were performed to analyze potential function of target genes of the DE miRNAs. The effects of candidate miRNAs modulated by METTL14 on cell migration and invasion abilities were confirmed by Transwell assays. We demonstrated that m6A methyltransferase METTL14 was significantly upregulated in BC tissues compared with normal tissues. METTL14 gain-and loss-of-expression regulated m6A levels in MCF-7 and MDA-MB-231 cells. The cell function assays revealed that METTL14 overexpression enhanced the migration and invasion capacities of BC cells. Moreover, treatment with the m6A inhibitor suppressed this enhanced cell migration and invasion. Additionally, aberrant expression of METTL14 reshaped the miRNA profile in BC cell lines. The remodeled DE miRNA/mRNA network was found to be most enriched in cancer pathways, and DE miRNAs were enriched in cell adhesion terms. hsa-miR-146a-5p modulated by METTL14 promoted cell migration and invasion. METTL14 modulates m6A modification and hsa-miR-146a-5p expression, thereby affecting the migration and invasion of breast cancer cells.

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Lung samples were prepared to investigate the perturbing effects of light absorption for quantifying the fluorescence signal of aluminum phthalocyanine tetrasulfonic acid (AlPCS). Standard solutions of known concentration and depth were imaged with different exposure times and analyzed. The intensity was found to be a linear function of concentration, depth, exposure time, and area. Mice were exposed to an aerosol of AlPCS with a mass median aerodynamic diameter of 390 nm and geometric standard deviation of 1.8. Images of intact lung lobes and lung homogenates were obtained and then analyzed to allow quantifying the concentration of AlPCS among the lung lobes and trachea. For the distribution of aerosols, the results indicate that the concentration was uniform among the different lobes. Combining the quantitative analysis of the concentration with image analysis of the area/thickness, the mass deposited in each lobe was readily determined. This approach provides a quantitative means to determine the selectivity of drug delivery to mouse lower respiratory tract.

Increasing evidence suggests the involvement of microRNA-381 (miR-381) in chemoresistance of cancer treatment. However, its function and molecular mechanisms in breast cancer chemoresistance are still not well elucidated. In the present study, we aimed to investigate the functional role of miR-381 in cisplatin (DDP) resistance of breast cancer and discover the underlying molecular mechanism. The expression levels of miR-381 and MDR1 were detected by quantitative real-time PCR (qRT-PCR) and Western blot analysis in breast cancer tissues and cell lines. The DDP sensitivity and cell apoptosis of breast cancer cells were determined by MTT assay and flow cytometric analysis, respectively. The relationship between miR-381 and MDR1 was explored by target prediction and luciferase reporter analysis. miR-381 was decreased in DDP-resistant breast cancer tissues and cell lines. Low miR-381 expression was correlated with poor prognosis of breast cancer patients. miR-381 overexpression improved DDP sensitivity of MCF-7/DDP and MDA-MB-231/DDP cells. Conversely, miR-381 inhibition lowered the response of MCF-7 and MDA-MB-231 to DPP. Moreover, miR-381 could directly suppress multidrug resistance 1 (MDR1) expression. MDR1 knockdown could overcome DDP resistance in MCF-7/DDP and MDA-MB-231/DDP cells, while MDR1 overexpression led to DDP resistance in MCF-7 and MDA-MB-231 cells. Notably, MDR1 overexpression counteracted the inductive effect of miR-381 mimics on DDP sensitivity of MCF-7/DDP and MDA-MB-231/DDP cells. On the contrary, miR-381 inhibition-mediated DDP resistance in MCF-7 and MDA-MB-231 cells was reversed by MDR1 knockdown. In summary, miR-381 could overcome DDP resistance of breast cancer by directly targeting MDR1, providing a novel therapeutic target for breast cancer chemoresistance.