ShRNA-mediated silencing of hTERT promote apoptosis and senescence in human ovarian cancer cells

shRNA介导的hTERT沉默促进人卵巢癌细胞凋亡和衰老。

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Abstract

BACKGROUND: Human telomerase reverse transcriptase (hTERT) is a crucial oncogene and a key factor in cell immortalization. Apart from hematopoiesis stem cell and germ cells, normal cells and tissues almost no expression of this gene. However, the positive expression rate of hTERT in malignant tumors is as high as 80-95%. This study was designed to investigate the mechanism of knockdown of hTERT expression in the regulation of ovarian cancer carcinogenesis in nude mice transplantation model. METHODS: We identified the function of hTERT in the treatment of ovarian cancer by constructing a nude mice transplantation tumor model. Then analyzed the mechanism of hTERT in modulating ovarian cancer cell apoptosis and senescence by immunohistochemically staining. RESULTS: Our analysis identified hTERT as a novel regulator of ovarian cancer progression and is one of the most significantly upregulated genes in ovarian cancer. Down-regulation of hTERT inhibits proliferation of ovarian cancer cells by promoting apoptosis and the expression of the senescence gene p53 and p21. CONCLUSIONS: hTERT is a key oncogene in ovarian tumorigenesis and metastasis; the downregulation of hTERT significantly inhibit the proliferation of ovarian cancer and have an effect on treatment of ovarian cancer by activating cell apoptosis and senescence pathway.

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