Identification of MicroRNAs Involved in Resistance to Sunitinib in Renal Cell Carcinoma Cells

被引:45
作者
Yamaguchi, Noriya [1 ,2 ]
Osaki, Mitsuhiko [1 ,3 ]
Onuma, Kunishige [1 ]
Yumioka, Tetsuya [2 ]
Iwamoto, Hideto [2 ]
Sejima, Takehiro [2 ]
Kugoh, Hiroyuki [3 ,4 ]
Takenaka, Atsushi [2 ]
Okada, Futoshi [1 ,3 ]
机构
[1] Tottori Univ, Div Pathol Biochem, Tottori, Japan
[2] Tottori Univ, Dept Surg, Div Urol, Fac Med, Tottori, Japan
[3] Tottori Univ, Chromosome Engn Res Ctr, Tottori, Japan
[4] Tottori Univ, Dept Biomed Sci, Inst Regenerat Med & Biofunct, Grad Sch Med Sci, Tottori, Japan
关键词
miRNA; renal cell carcinoma; sunitinib; tyrosine kinase inhibitor; SEQUESTRATION; METASTASIS; LYSOSOMES;
D O I
10.21873/anticanres.11652
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Aim: To generate sunitinib-resistant renal cell carcinoma (RCC) cell lines and identify miRNAs contributing to sunitinib resistance. Materials and Methods: Two RCC cell lines, ACHN and RCC23, were cultured by continuous treatment with sunitinib for 3 months, with doses gradually increasing up to the 50% inhibitory concentration for each cell line. We performed microarray and quantitative real-time polymerase chain reaction analyses of sunitinib-resistant ACHN (SR-ACHN) and RCC23 (SR-RCC23) cells, as well of as sunitinib-sensitive ACHN and RCC23 cells. Results: SR-ACHN and SR-RCC23 cells exhibited significantly higher resistance to sunitinib treatment compared to sunitinib-sensitive cells. SR-ACHN and SR-RCC23 cells were hypertrophic and contained granules in the cytoplasm. When SR-ACHN and SR-RCC23 cells were compared to ACHN and RCC23 cells, expression of miR-575, miR-642b-3p, and miR-4430 was significantly increased, while that of miR-18a-5p, miR-29b-1-5p, miR-431-3p, and miR-4521 was significantly decreased. Conclusion: These miRNAs may contribute to sunitinib resistance in humans.
引用
收藏
页码:2985 / 2992
页数:8
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