Background Circular RNAs (circRNAs) are a class of non-coding RNAs which function as novel regulators in human cancers. In this study, we aimed to investigate the functional roles and related molecular mechanisms of circ_0006282 in gastric cancer (GC) progression. Methods Fifty-five GC patients were enrolled in this study. GC cells (AGS and HGC-27) and normal cells (GES-1) were cultured in RPMI1640 added with 10% FBS and 1% penicillin-streptomycin. Quantitative real-time polymerase chain reaction (qRT-PCR) assay was used to determine the expression levels of circ_0006282, transcription elongation factor B subunit 1 (TCEB1) mRNA, miR-144-5p and tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein β (YWHAB; also known as 14-3-3β). RNase R assay was used to determine the characteristic of circ_0006282. Cell Counting Kit-8 (CCK-8) assay and colony formation assay were employed for cell proliferation. Transwell assay was conducted for cell migration and invasion. Western blot assay was carried out to measure the protein levels of Cyclin D1, matrix metalloprotein 9 (MMP9) and YWHAB. Dual-luciferase reporter assay, RNA pull-down assay and RIP assay were adopted to analyze the interaction between miR-144-5p and circ_0006282 or YWHAB. Murine xenograft model assay was performed to explore the function of circ_0006282 in vivo. Results Circ_0006282 level was increased in GC tissues and cells compared to normal tissues and cells. Silencing of circ_0006282 restrained GC cell proliferation, migration and invasion. For mechanism analysis, circ_0006282 was identified to function as the sponge for miR-144-5p to positively regulate YWHAB expression in GC cells. Moreover, miR-144-5p inhibition or YWHAB overexpression effectively reversed the impacts of circ_0006282 knockdown on GC cell growth and motility. Additionally, circ_0006282 knockdown blocked tumor growth of GC in vivo. Conclusion Circ_0006282 facilitated the malignant behaviors of GC cells through circ_0006282/miR-144-5p/YWHAB axis.

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Objective: To investigate the mechanism of apoptosis induced by myeloid cell leukemia-1 (Mcl-1) inhibitor UMI-77 on gallbladder carcinoma GBC-SD cells.Methods: GBC-SD cells were treated with different concentrations of UMI-77. GBC-SD cell proliferation and apoptosis were detected by MTT assay and Annexin V/PI. The expressions of Mcl-1, Bcl-2, Bcl-xL, Bax, Bak, cleaved-caspase 9, cleaved-caspase 3 and cleaved-PARP proteins in GBC-SD cells treated with UMI-77 were detected by Western blotting.Results: The results of MTT showed that different concentrations of UMI-77 had different inhibitory effects on cell proliferation of GBC-SD cells in a dose-dependent and time-dependent manner. Annexin V/PI results showed that the apoptosis rate was increasing gradually with the increase of UMI-77 concentration in a dose-dependent manner. Western blotting results showed that the expression of anti-apoptotic protein Mcl-1 was significantly decreased (p < .05), and the expressions of Bax and Bak proteins were significantly increased respectively (p < .05), but there were no significant changes in the expressions of Bcl-2 and Bcl-xL proteins, and the expression levels of cleaved-caspase 9, cleaved-caspase 3 and cleaved-PARP proteins were significantly increased (p < .05) in 24 h after GBC-SD cells were treated with 10 μmol/L of UMI-77.Conclusions: Mcl-1 inhibitor UMI-77 can induce the apoptosis of GBC-SD cells in a dose-dependent manner through the caspase-mediated endogenous apoptosis pathway. Therefore, Mcl-1 may become a new therapeutic target in the research on gallbladder cancer.