Wang Y

Gradient decrease in telomerase and its RNA in progressive passage of human endometrial stromal stem cells

Abstract The purpose of this study was to explore the change of telomerase in passage from human endometrial stromal stem cells isolated from human endometrium. Telomerase activity of cultured endometrial stromal cells was assessed at mRNA and protein levels using RT-PCR and immunohistochemistry technique. Telomerase mRNA and protein levels were higher at early passages, and then had a gradually decreased trend of immunoreactive intensity and gradually weakened positive cells with progressive passage in endometrial stromal stem cells. These results suggest that telomerase is contributed to the insenecence of endometrial stem cell.

miR-603 targeted hexokinase-2 to inhibit the malignancy of ovarian cancer cells

The Warburg effect, characterized by energy production through a high rate of aerobic glycolysis, is a metabolic hallmark of cancer cells. We previously found that ginsenoside 20(S)-Rg3 upregulated miR-603 and impaired the malignancy of ovarian cancer cells by inhibiting the Warburg effect. However, the precise functional role of miR-603 in ovarian cancer progression remains poorly defined. Here, we report that the level of miR-603 in ovarian cancer tissues is significantly lower than that in para-tumor tissues. Overexpression of miR-603 in ovarian cancer cells inhibits the Warburg effect as evidenced by a decrease in glucose consumption, lactate production and hexokinase-2 (HK2) expression, reduces cell proliferation in vitro, and weakens their migration and invasion. Further, miR-603 directly targets HK2 as indicated in a luciferase reporter assay. In contrast to agomiR-NC, agomiR-603 treatment significantly inhibits tumor growth in vivo and the Warburg effect, which is illustrated by a decreased uptake of 18F-FDG in subcutaneous xenografts and HK2 downregulation. Finally, miR-603 is negatively regulated by DNMT3A-mediated DNA methylation in the promoter region of its precursor gene, suggesting that 20(S)-Rg3 antagonizes DNMT3A-mediated DNA methylation to impair growth, migration and invasion of ovarian cancer cells. In conclusion, miR-603 is a tumor suppressor targeting HK2 in ovarian cancer and its low level may result from DNMT3A-mediated methylation.