miR-205 inhibits cell growth by targeting AKT-mTOR signaling in progesterone-resistant endometrial cancer Ishikawa cells
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Zhihong Zhuo1, Huimin Yu1
1Ningbo No. 2 Hospital, 315010 Ningbo, People’s Republic of China
Zhihong Zhuo, email: email@example.com
Keywords: microRNA, endometrial carcinoma, autophagy, progesterone resistance
Received: January 18, 2017 Accepted: February 20, 2017 Published: March 03, 2017
Purpose: miR-205 is significantly up-regulated in endometrioid adenocarcinoma. In this study, the significant anticancer effect of a miR-205 inhibitor was investigated in both endometrial carcinoma and progesterone-resistant endometrial carcinoma cells.
Results: Compared with Ishikawa endometrial cancer cells, miR-205 was expressed at higher levels in a progesterone-resistant (PR) sub-cell line. Inhibition of miR-205 suppressed the growth of cancer cells in a dose- and time-dependent manner. Moreover, the miR-205 inhibitor induced a marked increase in the percentage of Ishikawa-PR cells in G2/M phases and a decrease in the percentage of cells in G0/G1 and S phases. In addition, miR-205 inhibitor-treated tumor cells exhibited increased apoptosis. Moreover, miR-205 was found to negatively regulate PTEN expression and lead to autophagy and activation of the AKT/mTOR pathway in PR cells, and PTEN protein levels significantly decreased with development of progesterone resistance in endometrial cancer cells. Western blot assay showed up-regulated autophagy, as indicated by expression of LC3-II/LC3-I and beclin1, in Ishikawa cells; in particular, autophagy was markedly induced in PR cells treated with the miR-205 inhibitor.
Materials and Methods: We measured and analyzed cell growth curves with and without miR-205 inhibition with the MTT assay, miR-205 expression by qRT-PCR, cell cycle and apoptosis using annexin V/propidium iodide staining and flow cytometry, and autophagy, apoptosis, and AKT-mTOR signaling by western blotting.
Conclusions: Inhibition of miR-205, which targets the AKT-mTOR pathway, in endometrial cancer cells provides a potential, new treatment for PR endometrial carcinoma.
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