Abstract
Ovarian cancer is the second most common gynaecological malignancy, and microRNAs (miRNAs) play important role in the cancer development. Here, we found that the level of miR-200b/200a/429 was significantly increased in serum and tumor tissues of patients with stage-I ovarian cancer. Consistent with these results, we detected increased expression levels of miR-200b/200a/429 in ovarian cancer cell lines compared with the human nontumorigenic ovarian epithelial cell line T80. The overexpression of miR-200b/200a/429 in T80 cells stimulated proliferation and caused their growth in soft agar and tumor formation in nude mice. Furthermore, we determined that miR-200b/200a/429 targets inhibitor of growth family 5 (ING5) and that the overexpression of ING5 can block miR-200b/200a/429-induced T80 cell transformation and tumorigenesis. Our findings suggest that miR-200b/200a/429 may be a useful biomarker for the early detection of ovarian cancer and that miR-200b/200a/429 significantly contributes to ovarian cancer development through ING5.
Highlights
Ovarian cancer is one of the most common gynecologic tumors in the world, with estimated 238,700 new cases and 151,900 deaths in 2012 [1]. e 5-year survival rate of earlystage ovarian cancer patients is more than 92%; the 5-year survival rate of late-stage ovarian cancer patients is only 29%, suggesting that early diagnosis is crucial for patient survival [2]
We identified the upregulated expression of miR200b/200a/429 in the sera of patients with stage-I ovarian cancer compared with healthy controls. e upregulated expression of miR-200b/200a/429 was identified in stage-I ovarian cancer tissues compared with matched normal tissues. e ectopic expression of miR-200b/200a/ 429 caused tumor formation in nude mice injected with the nontumorigenic human ovarian epithelial cell line T80 by targeting inhibitor of growth family 5 (ING5)
To investigate the role of ING5 in miR-200b/ 200a/429-induced ovarian tumor formation, stably expressing miR-200b/200a/429 T80 cells were transfected with the ING5 expression vector or an empty vector and 5 × 106 cells in 100 μl of phosphate-buffered saline (PBS) were subcutaneously injected into 6-week-old female nude mice
Summary
Ovarian cancer is one of the most common gynecologic tumors in the world, with estimated 238,700 new cases and 151,900 deaths in 2012 [1]. e 5-year survival rate of earlystage ovarian cancer patients is more than 92%; the 5-year survival rate of late-stage ovarian cancer patients is only 29%, suggesting that early diagnosis is crucial for patient survival [2]. Studies have shown that miRNAs of the miR-200s family play different roles in different progression stages by targeting different genes, even in the same cancer [7]. Ese Journal of Oncology findings suggest that the role of the miR-200s family at different tumor progression stages is necessary to study. E dysregulated expression of miR-200s was detected previously, and its role in different stages of ovarian cancer progression has been studied, including chemoresistance and metastasis [10, 11]. We identified the upregulated expression of miR200b/200a/429 in the sera of patients with stage-I ovarian cancer compared with healthy controls. E upregulated expression of miR-200b/200a/429 was identified in stage-I ovarian cancer tissues compared with matched normal tissues. Our findings suggest that miR-200b/200a/429 significantly contributes to ovarian cancer development and has potential as a biomarker for detecting early-stage ovarian cancer
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