miR-130b Promotes Sunitinib Resistance through Regulation of PTEN in Renal Cell Carcinoma

Yohei Sekino; Naoya Sakamoto; Kazuhiro Sentani; Naohide Oue; Jun Teishima; Akio Matsubara; Wataru Yasui

doi:10.1159/000500605

miR-130b Promotes Sunitinib Resistance through Regulation of PTEN in Renal Cell Carcinoma

Oncology. 2019;97(3):164-172. doi: 10.1159/000500605. Epub 2019 Jun 13.

Authors

Yohei Sekino^{1

2}, Naoya Sakamoto¹, Kazuhiro Sentani¹, Naohide Oue¹, Jun Teishima², Akio Matsubara², Wataru Yasui³

Affiliations

¹ Department of Molecular Pathology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
² Department of Urology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
³ Department of Molecular Pathology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan, wyasui@hiroshima-u.ac.jp.

PMID: 31195398
DOI: 10.1159/000500605

Abstract

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.

Keywords: PTEN; Renal cell carcinoma; Sunitinib; miR-130b.

MeSH terms

Aged
Aged, 80 and over
Carcinoma, Renal Cell / genetics*
Carcinoma, Renal Cell / metabolism
Cell Line, Tumor
Dose-Response Relationship, Drug
Drug Resistance, Neoplasm / genetics*
Female
Gene Expression Regulation, Neoplastic*
Gene Knockout Techniques
Humans
Kidney Neoplasms / genetics*
Kidney Neoplasms / metabolism
Male
MicroRNAs / genetics*
Middle Aged
Neoplasm Grading
Neoplasm Staging
PTEN Phosphohydrolase / genetics*
PTEN Phosphohydrolase / metabolism
Sunitinib / pharmacology*

Substances

MIRN130 microRNA, human
MicroRNAs
PTEN Phosphohydrolase
PTEN protein, human
Sunitinib