Prognostic importance of epithelial-mesenchymal transition-related protein expression in gastric carcinoma

Objective. Neuroblastoma (NB) is a highly metastatic tumor in children that develops in the sympathetic nervous system and has a low curative rate. Saikosaponin A (SSA), an active ingredient isolated from the root of Radix Bupleuri, is a natural compound with various pharmacological activities and shows good application prospects in antitumors. This study investigated the antihuman NB activity of SSA and underlying mechanisms associated with its actions. Materials and Methods. The MTT method was used to detect the activity of SSA in inhibiting human NB cell SK-N-AS proliferation. Cell morphology was observed. The flow cytometry technology was used in analyzing the cell apoptosis rate. The Transwell assay evaluated cell migration and invasion following SSA treatment, apoptosis-related protein expression, and angiogenesis-related protein expression, and EMT-related proteins were detected by western blot analysis. Results. SSA showed an inhibitory effect on SK-N-AS cells with the IC50 values of 14.14 μM at 24 h and 12.41 μM at 48 h. Results indicated that SSA has proapoptotic activity, and its proapoptotic activity is positively correlated with the Bax/Bcl-2/caspase-9/caspase-7/PARP pathway. Furthermore, SSA inhibited the invasion and migration of SK-N-AS cells via regulating the angiogenesis-related VEGFR2/Src/Akt pathway and the epithelial-mesenchymal transition- (EMT-) related protein expression. Conclusion. SSA exerts an antihuman NB effect and thus provides foundations for NB treatment.

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miR-203 inhibits arecoline-induced epithelial-mesenchymal transition by regulating secreted frizzled-related protein 4 and transmembrane-4 L six family member 1 in oral submucous fibrosis

Oncology Reports ◽

10.3892/or.2015.3909 ◽

2015 ◽

Vol 33 (6) ◽

pp. 2753-2760 ◽

Cited By ~ 16

Author(s):

LIAN ZHENG ◽

XINCHUN JIAN ◽

FENG GUO ◽

NING LI ◽

CANHUA JIANG ◽

...

Keyword(s):

Family Member ◽

Epithelial Mesenchymal Transition ◽

Oral Submucous Fibrosis ◽

Related Protein ◽

Mesenchymal Transition ◽

Submucous Fibrosis

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miR-33a Mediates the Anti-Tumor Effect of Lovastatin in Osteosarcoma by Targeting CYR61

Cellular Physiology and Biochemistry ◽

10.1159/000495396 ◽

2018 ◽

Vol 51 (2) ◽

pp. 938-948 ◽

Cited By ~ 5

Author(s):

Yazeng Huang ◽

Jun Zhang ◽

Haiyu Shao ◽

Jianwen Liu ◽

Mengran Jin ◽

...

Keyword(s):

Protein Expression ◽

Cell Invasion ◽

Epithelial To Mesenchymal Transition ◽

Regulatory Element ◽

Luciferase Reporter Assay ◽

Luciferase Reporter ◽

Osteosarcoma Cell ◽

Reporter Assay ◽

Related Protein ◽

Mesenchymal Transition

Background/Aims: Preventing cell metastasis is an effective therapeutic strategy to treat osteosarcoma and improve prognosis. Statins have been found to have anticancer effects in addition to their cholesterol-lowering action. As a new target of statins, cysteine-rich 61 (CYR61) was recently identified to promote cell migration and metastasis in osteosarcoma. However, the underlying mechanisms mediating the regulation of CYR61 expression by statins remain unknown. Methods: Human osteosarcoma cell lines MG63 and SaOS2 were used to clarify the effect of lovastatin on CYR61 expression. Real-time PCR was performed to detect mRNA or microRNA (miRNA) levels and western blot was performed to detect protein levels. Cell invasive ability was determined using Transwell assays. Lentivirus encoding CYR61 cDNA or sterol regulatory element-binding protein 2 (SREBP-2) shRNA was used to upregulate CYR61 expression or downregulate SREBP-2 expression. Binding of the CYR61 3’ untranslated region (UTR) and miR-33a was analyzed by luciferase reporter assay. Results: We found that lovastatin treatment decreased CYR61 expression, inhibited cell invasion and altered epithelial-to-mesenchymal-transition (EMT)-related protein expression, while CYR61 overexpression abolished the effect of lovastatin. Moreover, lovastatin increased the expression of SREBP-2 and miR-33a, which were then downregulated by SREBP-2 silencing. Bioinformatics analysis indicated that the CYR61 3′UTR harbored a potential miR-33a binding site and luciferase reporter assay demonstrated that CYR61 was a target of miR-33a in osteosarcoma cells. Furthermore, miR-33a could inhibit cell invasion and alter EMT-related protein expression. SREBP-2 silencing or miR-33a inhibitor upregulated CYR61 expression and reversed the effects of lovastatin on cell invasion and EMT-related proteins. Conclusion: Our findings suggest lovastatin suppresses osteosarcoma cell invasion through the SREBP-2/miR-33a/CYR61 pathway.

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