DEP Domain Containing 1 Promotes Proliferation, Invasion, and Epithelial-Mesenchymal Transition in Colorectal Cancer by Enhancing Expression of Suppressor of Zest 12.

Objective: DEP domain containing 1 (DEPDC1), aberrantly upregulated in various tumors, has been shown to be involved in the occurrence and development of tumors. This study aims to investigate pathophysiological roles of DEPDC1 in colorectal cancer (CRC). Materials and Methods: Expression level of DEPDC1 and suppressor of zest 12 (SUZ12) in CRC tissues and cell lines were analyzed by quantitative real-time polymerase chain reaction and immunohistochemistry. Staining with 5-bromo-2-deoxyuridine staining and colony formation assays were conducted to evaluate cell proliferation. Transwell or wound healing assay to evaluate invasion or migration, respectively. The effect on epithelial-mesenchymal transition (EMT) of CRC was determined by Western blot. Results: DEPDC1 and SUZ12 were increased in CRC tissues and cell lines. Silence of DEPDC1 suppressed cell proliferation, migration, and invasion of CRC. Moreover, DEPDC1 knockdown suppressed EMT of CRC. Mechanistically, the authors demonstrated silencing DEPDC1 decreased protein expression of SUZ12 and led to a remarkable reduction of trimethylation on the lysine 27 residue of histone H3 (H3K27Me3). Inhibitory ability of DEPDC1 knockdown on CRC progression was reversed by overexpression of SUZ12. Conclusions: DEPDC1 promoted CRC progression through regulation of SUZ12-mediated H3K27Me3, illuminating a novel DEPDC1-SUZ12 molecular axis as regulator in CRC progression and suggesting potential implications in treatment of CRC.

Effects of aspirin on hepatocellular carcinoma and its potential molecular mechanism.

PURPOSE: To explore the effects of aspirin (ASP) on the proliferation and apoptosis of HepG2 hepatocellular carcinoma (HCC) cells via the Wnt/ß-catenin signaling pathway. METHODS: Human HCC cells were cultured and treated with ASP at different concentrations. Cell proliferation was determined with cell counting kit-8 (CCK-8) and colony formation, and the rate of apoptosis was measured by flow cytometry. Western blotting (WB) and quantitative polymerase chain reaction (qRT-PCR) assays were used to assess the changes in the expression levels of related proteins. RESULTS: ASP showed a time-and concentration-depented inhibitory effect on HepG2 cell proliferation. The number of colonies formed in ASP-treated HCC cells was significantly lower than in control cells. For HCC cells treated with ASP, the apoptosis rate enhanced with the increase of ASP concentration. The expression levels of TCF4 and LEF1, key molecules of the Wnt/ß-catenin signaling pathway, were lowered in HCC cells treated with 4 mM ASP, and the nuclear translocation of ß-catenin was weakened. The ß-catenin activator exerted a negative influence on the anticancer effect of ASP. CONCLUSIONS: ASP inhibits the proliferation and promotes the apoptosis of HCC cells through the Wnt/ß-catenin signaling pathway.

MicroRNA-182 promotes proliferation and metastasis by targeting FOXF2 in triple-negative breast cancer.

Triple-negative breast cancer (TNBC), the most aggressive subtype of breast cancer (BC), is characterized as high proliferation, young age and poor prognosis. MicroRNA-182 (miR-182) was reported to have oncogenic potential in many cancers. We aimed to elucidate pathobiological effects of miR-182 expression by targeting forkhead-box F2 (FOXF2) in TNBC. In this study, we explored the functional role of miR-182 expression in TNBC. Quantitative real-time PCR (qRT-PCR) was applied to evaluate the expression of miR-182 in cell lines and tissues. A series of in vitro and in vivo assays were performed in the MCF-7 and MDA-MB-231 cell lines with miR-182 overexpression. Luciferase reporter assays and western blot analysis were used to identify FOXF2 as the direct and functional target of miR-182. In TNBC tissues and cell lines, we found that miR-182 was significantly upregulated. Transwell assay showed that re-expression of miR-182 increased cell migration and invasion abilities and MTT assay showed that it promoted cell growth in vitro. In vivo assay, re-expression of miR-182 significantly increase tumor volume and enhanced instant metastasis in the lungs of mice. Besides, FOXF2 was identified as a direct and functional target of miR-182. These results indicated that miR-182 plays an important role in the initiation and progression of TNBC by targeting FOXF2 and the miR-182/FOXF2 axis may present a new therapeutic strategy for TNBC in the future.