Paclitaxel exposure downregulates miR-522 expression and its downregulation induces paclitaxel resistance in ovarian cancer cells

Autor:	Aasa Shimizu, Tadashi Kimura, Masaki Kobayashi, Misa Yamamoto, Kyoso Ishida, Koji Nakamura, Akihiko Yoshimura, Kenjiro Sawada, Kae Hashimoto, Michiko Kodama, Mayuko Miyamoto
Jazyk:	angličtina
Rok vydání:	2020
Předmět:	Paclitaxel Down-Regulation lcsh:Medicine Carcinoma Ovarian Epithelial Article chemistry.chemical_compound Downregulation and upregulation Cell Line Tumor microRNA medicine Humans lcsh:Science Cancer genetics Cancer E2F2 Gynaecological cancer Ovarian Neoplasms Multidisciplinary biology Chemistry lcsh:R Retinoblastoma protein medicine.disease Antineoplastic Agents Phytogenic In vitro Gene Expression Regulation Neoplastic MicroRNAs Drug Resistance Neoplasm Cell culture biology.protein Cancer research Female lcsh:Q Ovarian cancer
Zdroj:	Scientific Reports, Vol 10, Iss 1, Pp 1-13 (2020) Scientific Reports
ISSN:	2045-2322
Popis:	Paclitaxel resistance is a critical challenge in ovarian cancer treatment. This study aimed to identify microRNAs (miRNAs) that modulate paclitaxel resistance for use as potential therapeutic targets in such settings. Paclitaxel-resistant cell lines were established using two ovarian cancer cell lines: SKOV3ip1 and HeyA8. The evaluation of miRNA polymerase chain reaction (PCR) arrays indicated that the expression of miR-522-3p was downregulated in paclitaxel-resistant cells. The restoration of miR-522-3p sensitized the resistant cells to paclitaxel, and its downregulation desensitized the parental cells. Using PCR arrays, we focused on E2F2, with the luciferase reporter assay revealing that it was a direct target for miR-522-3p. The paclitaxel-resistant cells showed stronger E2F2 expression than the parental cells, while E2F2 inhibition sensitized the resistant cells to paclitaxel. Forced E2F2 expression in the parental cells led to the acquisition of paclitaxel resistance, while miR-522-3p inhibited E2F2 expression and was associated with retinoblastoma protein phosphorylation attenuation, which resulted in G0/G1 arrest. The effects of miR-522-3p and E2F2 in ovarian cancer were examined using public databases, revealing that low miR-522-3p expression and high E2F2 expression were associated with significantly poorer overall survival. In conclusion, miR-522-3p attenuated the degree of paclitaxel resistance in vitro through the downregulation of E2F2; miR-522-3p supplementation may be a therapeutic target for paclitaxel-resistant ovarian cancer.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::91a256413c61e24aeb1089149f3002ec http://link.springer.com/article/10.1038/s41598-020-73785-8 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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