MicroRNA-17-92 gene promotes renewal and proliferation of gastric cancer stem cells

doi:10.3969/j.issn.2095-4344.2015.50.008

Abstract

Abstract:

BACKGROUND: Studies have shown that microRNAs (miRNAs) have moderating effect on the renewal and differentiation of cancer stem cells. However, there is no complete understanding on the effect of microRNA-17-92 gene on gastric cancer stem cell renewal and proliferation.
OBJECTIVE: To explore the effect of miRNA-17-92 in promoting self-renewal and proliferation of gastric cancer stem cells.
METHODS: (1) The gradually reduced miRNAs during gastric cancer stem cell self-renewal were investigated using miRNA array based on RNAs from differentiated and adherent cells. (2) The miRNA-17-92 was constructed and transfected to gastric cancer stem cells. (3) The effects of miRNA-17-92 on the self-renewal of gastric cancer stem cells were studied by tumor sphere assay in vitro. (4) The effects of miRNA-17-92 on the proliferation of
gastric cancer stem cells were investigated by MTT assay and colony formation assay.
RESULTS AND CONCLUSION: (1) miR-19b/20a/92a expression gradually reduced in the adhesion and differentiation of gastric cancer stem cells. (2) The expression of lentivirus carrying miRNA-17-19 gene in MKN28 cells and CD44-/EpCAM- cells were significantly increased; transient transfection of pre-miR-19b/20a/92a increased the expression of CD44-/EpCAM- and MKN28 miRNA, transient transfection of pre-miR-19b/20a/92a antagonists reduced the expression of SGC7901 and CD44+/EpCAM+ miRNA; overexpression of lenti-miR-19b/20a/92a significantly increased the ability of gastric cells to form tumor spheres; chemotherapy drugs prolonged the survival time of lenti-miR-19b/20a/92a-infected cells; transient transfection of pre-miR-19b/20a/92a significantly increased the number of CD44+/EpCAM+ cells, but transfection of pre-miR-19b/20a/92a antagonist reduced the number of CD44+/EpCAM+ cells. (3) MTT proliferation assay showed that gastric cancer cell proliferation rate in miR-19b/20a/92a stably expressing group was faster than that in the control group. Transient transfection of miR-19b/20a/92a precursor accelerated the growth rate of gastric cancer cells, and transient transfection of its antagonist slowed down the growth rate of gastric cancer cells. Colony formation assay showed that transient transfection of miR-19b/20a/92a precursor significantly increased the colony formation number as compared with the control group; transient transfection of miR-19b/20a/92a antagonist reduced the colony formation as compared with the control group. These findings indicate that miR-19b/20a/92a gene presents with continuous deletion in gastric cancer stem cell differentiation process, and miRNA-17-92 gene can promote the renewal and proliferation of gastric cancer stem cells.

中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

CLC Number:

R394.2

Song Zi-zheng, Yang Hua, Shang Yan-hong, Liu Bin, Zhang Gang,Wang Hua, Zang Ai-min. MicroRNA-17-92 gene promotes renewal and proliferation of gastric cancer stem cells[J]. Chinese Journal of Tissue Engineering Research, 2015, 19(50): 8077-8083.

Figures/Tables 9

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