@phdthesis{oai:ir.kagoshima-u.ac.jp:00016254,
 author = {玉井, 元規 and Tamai, Motoki},
 month = {2022-11-08, 2022-10-27, 2022-10-28, 2022-10-28},
 note = {博士論文全文, 博士論文要旨, 最終試験結果の要旨, 論文審査の要旨, Patients with advanced bladder cancer are generally treated with a combination of chemotherapeutics, including gemcitabine, but the effect is limited due to acquisition of drug resistance. Thus, in this study, we investigated the mechanism of gemcitabine resistance. First, gemcitabine-resistant cells were established and resistance confirmed in vitro and in vivo. Small RNA sequencing analyses were performed to search for miRNAs involved in gemcitabine resistance. miR-99a-5p, selected as a candidate miRNA, was downregulated compared to its parental cells. In gain-of-function studies, miR-99a-5p inhibited cell viabilities and restored sensitivity to gemcitabine. RNA sequencing analysis was performed to find the target gene of miR-99a-5p. SMARCD1 was selected as a candidate gene. Dual-luciferase reporter assays showed that miR-99a-5p directly regulated SMARCD1. Loss-of-function studies conducted with si-RNAs revealed suppression of cell functions and restoration of gemcitabine sensitivity. miR-99a-5p overexpression and SMARCD1 knockdown also suppressed gemcitabine-resistant cells in vivo. Furthermore, β-galactosidase staining showed that miR-99a-5p induction and SMARCD1 suppression contributed to cellular senescence. In summary, tumor-suppressive miR-99a-5p induced cellular senescence in gemcitabine-resistant bladder cancer cells by targeting SMARCD1.

Motoki Tamai, Shuichi Tatarano, Shunsuke Okamura, Wataru Fukumoto, Issei Kawakami, Yoichi Osako, Takashi Sakaguchi, Satoshi Sugita, Masaya Yonemori, Yasutoshi Yamada, Masayuki Nakagawa, Hideki Enokida, Hirofumi Yoshino
microRNA-99a-5p induces cellular senescence in gemcitabine-resistant bladder cancer by targeting SMARCD1
Molecular Oncology 16(6), 1329-1346 (2022)
https://doi.org/10.1002/1878-0261.13192},
 school = {鹿児島大学},
 title = {microRNA-99a-5p induces cellular senescence in gemcitabine-resistant bladder cancer by targeting SMARCD1},
 year = {},
 yomi = {タマイ, モトキ}
}