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Cell Journal، جلد ۱۶، شماره Suppl ۱، صفحات ۱۲۲-۱۲۲
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عنوان انگلیسی Ps-91: ES Cell-Specific miR-302 Reprograms Skin and Colon Cancer Cells, and Modulates Apoptosis, Metastasis and Angiogenesis Markers
چکیده انگلیسی مقاله Objective: The miR-302 cluster is the most abundantly expressed miRNA in human embryonic stem cells which is subsequently down-regulated during the process of differentiation. Previous studies have shown that transfection of some cancer cell lines with miR- 302 expressing vectors can reprogram these cells and transform them into an embryonic stem-like state with a lower proliferation rate. Materials and Methods: In the current study, melanoma A-375 and colorectal adenocarcinoma HT- 29 cancer cell lines were transfected with pEGFPC1- miR-302a/b/c/d and mock vectors. The expression of some pluripotency, apoptotic, invasion, and angiogenesis genes was evaluated by RT-PCR and quantitative real-time PCR. Furthermore, the expression of Oct4 and Sox2 proteins was assessed by immunocytochemistry. Cell cycle analysis was performed by propidium iodide (PI) flowcytometric assay. Results: The pluripotency markers were upregulated after transfection with miR-302 cluster. According to the cell cycle analysis, a significant proportion of the A- 375-miR-302 cells were arrested in G2 phase, and apoptosis was induced in about eight percent of the cells. Moreover, the expression of some apoptotic genes was increased in A-375 cell line. There was no significant cell death after transfection of HT-29 cell line with miR-302 cluster while the proliferation rate was mildly decreased. Additionally, the expression of some apoptotic and cell cycle regulator genes in HT-29 cell line was upregulated following miR-302 transfection. There was also an upregulation of CDH1 and downregulation of SNAIL, HIF1A, and VEGFA in both cell lines. However, the expression levels of MMP2, HIF1B, and DLL4 were decreased exclusively in the A-375 cell line. Increased expression of MMP2 and DLL4 genes in HT-29 cell line was one of the most controversial observations in this study. Conclusion: Results of this study revealed that transfection of A-375 and HT-29 cancer cells by miR-302 cluster can upregulate the expression of pluripotency genes in both cell lines. Moreover, this cluster can induce cell cycle arrest and apoptosis primarily in the melanoma cell line. Furthermore, overexpression of miR-302 cluster may disrupt various signaling pathways which are involved in different stages of metastasis and angiogenesis through modulation of particular target mRNAs.
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نشانی اینترنتی http://celljournal.org/journal/article/abstract/416
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