miR-130b Promotes Sunitinib Resistance through Regulation of PTEN in Renal Cell Carcinoma
Autor: | Yohei Sekino, Jun Teishima, Naoya Sakamoto, Naohide Oue, Kazuhiro Sentani, Akio Matsubara, Wataru Yasui |
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Rok vydání: | 2019 |
Předmět: |
Male
Cancer Research Biology urologic and male genital diseases 03 medical and health sciences Gene Knockout Techniques 0302 clinical medicine Cell Line Tumor microRNA medicine Sunitinib PTEN Humans MTT assay 030212 general & internal medicine Carcinoma Renal Cell Aged Neoplasm Staging Aged 80 and over Gene knockdown Dose-Response Relationship Drug Cell growth PTEN Phosphohydrolase General Medicine Middle Aged female genital diseases and pregnancy complications Kidney Neoplasms Reverse transcription polymerase chain reaction Gene Expression Regulation Neoplastic MicroRNAs Oncology Cell culture Drug Resistance Neoplasm 030220 oncology & carcinogenesis Cancer research biology.protein Female Neoplasm Grading medicine.drug |
Zdroj: | Oncology. 97(3) |
ISSN: | 1423-0232 |
Popis: | Background: MicroRNAs are a class of small noncoding RNAs that play an important role in progression and drug resistance in cancer. Several reports have shown that miR-130b modulates cell growth and drug resistance in some cancers. However, the expression and biological role of miR-130b in renal cell carcinoma (RCC) remain poorly understood. This study aimed to examine the expression and functional role of miR-130b and to analyze the association between miR-130b and sunitinib resistance in RCC. Methods: The expression of miR-130b in 32 RCC tissues and their corresponding normal kidney tissues was determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR). We performed a 4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT) assay in RCC cell lines transfected with miR-130b inhibitor or miR-130b mimics. We evaluated the relationship between miR-130b and PTEN and also analyzed the effect of miR-130b on sunitinib resistance. Results: qRT-PCR analysis showed that the expression of miR-130b was higher in RCC tissues than in corresponding normal kidney tissues. The MTT assay revealed that miR-130b modulated cell growth. qRT-PCR revealed an inverse correlation between miR-130b and PTEN in RCC. Western blotting demonstrated that miR-130b regulated the expression of PTEN in the RCC cell line. Additionally, miR-130b was associated with sunitinib resistance through regulation of PTEN. We established the sunitinib-resistant Caki-1 (Caki-1-SR) cells and observed that the expression of miR-130b was elevated in Caki-1-SR cells compared with parental Caki-1 cells. Knockdown of miR-130b improved sunitinib resistance in Caki-1-SR cells. Conclusion: The expression of miR-130b was upregulated in RCC. miR-130b promoted cell growth and was associated with sunitinib resistance through regulating PTEN expression. Collectively, these results suggest that miR-130b may play an oncogenic role and be a promising therapeutic target. |
Databáze: | OpenAIRE |
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