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MicroRNAs (miRNAs) are known to be important in a variety of cancer types. The specific expression and roles of miR-520f-3p in the context of gastric cancer (GC), however, remains unknown. Herein we determined miR-520f-3p expression to be significantly reduced in human GC cells compared to cells of the gastric epithelium, with comparable down-regulation also being evident in gastric cancer tissue samples and the low expression of this miRNA was positively correlated with features of more aggressive large tumor size (p = 0.019), depth of invasion (p = 0.008), and distant metastasis (p = 0.037). We further found that lower levels of miR-520f-3p corresponded with poorer GC patient overall (p = 0.003) and disease-free (p = 0.036) survival. When over-expressed in GC cells, miR-520f-3p was able to impair their growth, proliferation, and survival, instead leading to the induction of apoptosis. We further found that miR-520f-3p was able to bind the SOX9 3′-UTR, thereby negatively regulating its expression in GC cells. Consistent with this model, SOX9 and miR-520f-3p expression were negatively correlated with one another in GC tissues. When SOX9 was upregulated, this was also able to abrogate miR-520f-3p-mediated inactivation of Wnt/β-catenin signaling. Together our findings thus suggest that miR-520f-3p can act to suppress GC progression, at least in part via suppressing SOX9 expression and thus disrupting Wnt/β-catenin signaling. Our results thus highlight potential novel therapeutic targets in GC worthy of future investigation. [ABSTRACT FROM AUTHOR]

Background/Aims: Current practical advances in high-throughput data technologies including RNA-sequencing have led to the identification of long non-coding RNAs (lncRNAs) for potential clinical application against bladder urothelial cancer (BLCA). However, most previous studies focused on the clinical value of individual lncRNAs, which has limited the potential for future clinical application. Methods: In this study, RNA-sequencing data of lncRNAs was downloaded from The Cancer Genome Atlas database. Risk score was constructed based on survival-associated lncRNAs identified using differential expression analysis as well as univariate and multivariate Cox proportional hazards regression analysis. Receiver operating characteristic and Kaplan-Meier curve analyses were employed to evaluate the clinical and prognostic value of risk scores. Bioinformatics analyses were used to investigate the potential mechanisms of newly identified lncRNAs. Results: Among 2,127 differentially expressed lncRNAs (DELs), four new lncRNAs (AC145124.1, AC010168.2, MIR200CHG, and AC098613.1) showed valuable prognostic effects in BLCA patients. More importantly, the four-DEL-based risk score had the potential to become an independent marker for the survival status prediction of BLCA patients. Distinct co-expressed genes and signaling pathways were identified when BLCA was categorized into low- and high-risk groups. Furthermore, a protein-coding gene, HIST4H4 was found only 68 bp from the AC010168.2 DEL. HIST4H4 expression level was evidently up-regulated and positively correlated with AC010168.2 in BLCA patients. Conclusion: This in silico investigation pioneers the future investigation of the utility of prognostic lncRNAs for BLCA. [ABSTRACT FROM AUTHOR]

Introduction: Dynamin 3 (DNM3) is a large GTPase that possesses mechanochemical properties and has been shown to be involved in malignancies. However, most studies about DNM3 are observational, and knowledge of the precise molecular mechanism of DNM3 remains limited. Materials and methods: We constructed a PCDH-CMV-MCS-EF1a-GFP-Puro-DNM3 recombinant eukaryotic expression vector, which was then transfected into SW620 and LoVo cells. One cell line was divided into three groups. DNM3 mRNA and protein expression was analyzed by quantitative real-time PCR and Western blot assay. To investigate DNM3 biological activity in colon cancer SW620 and LoVo cell line, we performed cell proliferation, transwell migration, and invasion assay. Matrix metalloproteinase (MMP)-2 and MMP-9 protein expressions were detected by Western blot. Result: We successfully constructed a PCDH-CMV-MCS-EF1a-GFP-Puro-DNM3 recombinant eukaryotic expression vector, and stable DNM3 expression was observed in SW620 and LoVo cell lines. The vector overexpressing DNM3 inhibited the proliferation, weak invasion, and migration ability of colon cancer SW620 and LoVo cells relative to those in the control group (all P,0.001). DNM3 downregulated the protein expression of MMP-2 and MMP-9. Conclusion: DNM3 may weaken the malignant behavior of colon cancer and may have promoted the invasion and migration of colon cancer by regulating the expression of MMP-2 and MMP-9. [ABSTRACT FROM AUTHOR]

[Display omitted] • Various acridone derivatives were synthesized and evaluated for anticancer activity. • C4 exhibited potent activity against Hep-G2 cells with IC 50 value of 6.29 ± 0.93 μM. • C4 could specifically bind to and destabilize Kras gene promoter i-motif structure. • C4 down-regulated Kras gene expression possibly through its promoter i-motif. • C4 induced cell apoptosis possibly related to its effect on mitochondrial dysfunction. Two series of novel acridone derivatives were designed and synthesized, with their anticancer activity evaluated. Most of these compounds showed potent antiproliferative activity against cancer cell lines. Among them, compound C4 with dual 1,2,3-triazol moieties exhibited the most potent activity against Hep-G2 cells with IC 50 value determined to be 6.29 ± 0.93 μM. Subsequent experiments showed that C4 could bind to and destabilize Kras gene promoter i-motif structure without significant interaction with its corresponding G-quadruplex. C4 could down-regulate Kras expression in Hep-G2 cells, possibly due to its interaction with the Kras i-motif. Further cellular studies indicated that C4 could induce apoptosis of Hep-G2 cells, possibly related to its effect on mitochondrial dysfunction. These results indicated that C4 could be further developed as a promising anticancer agent. [ABSTRACT FROM AUTHOR]

Abstract: A series of 1,8-dipyrazolcarbazole (DPC) derivatives (6a–6d, 7a–7d) designed as G-quadruplex ligands have been synthesized and characterized. The FRET-melting and SPR results showed that the DPC derivatives could well recognize G-quadruplex with strong discrimination against the duplex DNA. In addition, the DPC derivatives showed much stronger stabilization activities and binding affinities for c-myc G-quadruplex rather than telomeric G-quadruplex. Therefore, their interactions with c-myc G-quadruplex were further explored by means of CD spectroscopy, PCR-stop assay, and molecular modeling. In cellular studies, all compounds showed strong cytotoxicity against cancer cells, while weak cytotoxicity towards normal cells. RT-PCR assay showed that compound 7b could down-regulate c-myc gene expression in Ramos cell line, while had no effect on c-myc expression in CA46 cell line with NHE III1 element removed, indicating its effective binding with G-quadruplex on c-myc oncogene in vivo. [Copyright &y& Elsevier]

Abstract: A series of icariin derivatives were synthesized. Their multidrug resistance (MDR) reversal activities were evaluated by MTT assay and the results indicated that the derivatives were the potent modulators of MDR. It was showed that the derivatives significantly increased the intracellular accumulation of ADR in MCF-7/ADR cells compared with drug sensitive MCF-7 cells. The results of bi-directional assay and reverse transcription polymerase chain reaction (RT-PCR) assay showed that the derivatives had high inhibitory activity against P-gp efflux function and significantly down-regulated on the expression of P-gp. [Copyright &y& Elsevier]