BACKGROUND: Non-small cell lung cancer (NSCLC) is the most common cancer worldwide. Circular RNAs (circRNAs) are recently identified as important gene regulators with critical roles in cancer biology. In this study, we focus on the effect of circ_0000376 targeting miR-384 on malignant phenotypes of NSCLC cells. METHODS: Circ_0000376 and miR-384 expression in NSCLC tissue samples were measured using qRT-PCR. The association between pathological parameters and the circ_0000376 expression was analyzed as well. Human NSCLC cell lines A549 and NCI-H460 were used as cell models. CCK-8 and BrdU assay were used to assess the effect of circ_0000376 on NSCLC cell line proliferation and drug sensitivity. Transwell assay was conducted to detect the effect of circ_0000376 on migration and invasion. Further, luciferase reporter assay was employed to validate the targeting of miR-384 by circ_0000376. RESULTS: Circ_0000376 expression in NSCLC clinical samples was up-regulated and this was linked to unfavorable pathological parameters. Circ_0000376 markedly accelerated the proliferation and metastasis, and enhanced chemoresistance of NSCLC cells. Mechanically, circ_0000376 overexpression could bind with miR-384 and repress its expression. CONCLUSIONS: Circ_0000376 is a newly discovered oncogenic circRNA in NSCLC, and can be potentially regarded as a diagnostic biomarker and therapy target.

Increasing evidence confirms that exosome-mediated transfer of microRNAs can influence cancer progression including tumor cell invasion, cell proliferation, and drug resistance via cell-cell communication. However, the potential role of exosomal-miR-1260b in lung adenocarcinoma (LAC) remains poorly understood.Thus, this study focused on investigating the function of exosomal-miR-1260b on cell invasion. Exosomal-miR-1260b was found to be higher in plasma of patients with LAC than that of healthy persons via quantitative real-time polymerase chain reaction assay. The sensitivity and specificity of exosomal-miR-1260b (cutoff point: 2.027) were 72% and 86%, and area under the curve of 0.845 (95% CI = 0.772-0.922). Elevated expression of miR-1260b in LAC tissues was positively correlated with exosomal-miR-1260b in plasma (r = .642, p < .05). Furthermore, ceramide biosynthesis regulated exosomal-miR-1260b secretion. Exosomemediated transfer of miR-1260b promoted A549 cell invasion and was still functional inside A549 cells. Moreover, exosomal-miR-1260b regulated Wnt/ β-catenin signaling pathway by inhibiting sFRP1 and Smad4. This study identified a new regulation mechanism involving in cell invasion by exosome-mediated tumorcell-to-tumor-cell communication. Targeting exosome-microRNAs may provide new insights into the diagnosis and treatment of LAC.

Protoporphyrin IX (PpIX) is used as a photosensitizer in the photodynamic diagnosis (PDD) and photodynamic therapy (PDT) of cancer and is synthesized intracellularly from 5-aminolevulinic acid (5-ALA) precursors. Thirteen novel 5-ALA derivatives were designed and synthesized appropriately with tailored hydrophilicity and lipophilicity. The generation of PpIX was detected and their antitumor activity in vitro and in vivo was also investigated. It was shown that compounds 9b-c, 11b-c and 13a displayed a characteristic long wavelength absorption peak at 593 nm after 5 h incubation in mice fibrosarcoma S180 cells. After being exposed to 600 nm laser light irradiation, these compounds can inhibit cell proliferation in S180 cells in vitro. The growth of S180 cell tumors in Kunming mice was significantly inhibited by these compounds in vivo. Among these compounds, 13a has low dark toxicity and high phototoxicity, which makes it an effective and promising prodrug for PDT.

Background Cisplatin-resistant gastric cancer (GC) occurs in patients with GC treated with cisplatin-based chemotherapy, which results in disease progression and early recurrence during the treatment. Material/Methods To understand the initiation and developmental mechanism underlying cisplatin-resistant GC, we developed cisplatin-resistant SGC7901 cells (SGC7901/DDP) from the parental cells (SGC7901/S) by continuous exposure to increasing concentrations of cisplatin and subjected these 2 cell lines to RNA sequencing analysis. The data were verified by quantitative polymerase chain reaction and their functional role was evaluated by cell counting kit 8 assay and cell apoptosis and cell cycle flow cytometric analysis. Bioinformatics analysis was performed to classify the differentially-expressed genes (DEGs) involved in the development of cisplatin resistance. Results In comparison with SGC7901/S cells, SGC7901/DDP cells showed a total of 3165 DEGs (2014 upregulated and 1151 downregulated, fold change ≥2, and adjusted P value <0.001). qRT-PCR confirmed the reliability of the RNA sequencing results. Depletion of the top 5 upregulated mRNAs reversed the resistant index, increased apoptotic SGC7901/DDP cells, and arrested the cells at G2/M phase. Gene ontology analysis revealed that the DEGs mainly regulate metabolic process, immune system, locomotion, cell adhesion, cell growth, cell death, cytoskeleton organization, cell binding, signal transducing activity, and antioxidant activity. Kyoto Encyclopedia of Genes and Genomes analysis showed that the DEGs were mainly involved in the PI3K-Akt signaling pathway, Rap1 signaling pathway, proteoglycans in cancer, regulation of actin cytoskeleton, and pathways in cancer. Concluisons The present study is the first to interrogate mRNAs profiles in human GC cells with cisplatin resistance using RNA sequencing, which may assist in discovering potential therapeutic targets for cisplatin-resistant GC patients.