Abstract
BackgroundATP-binding cassette transporter super-family including ABCC1 and MDR-1 were involved in multi-drug resistance (MDR) of renal cell carcinoma (RCC) patients. Several miRNAs were confirmed to promote the MDR and the survival of tumor cells.MethodsThe RCC cell lines Caki-2 with vinblastine-resistant (Caki-2/VBL) or doxorubicin-resistant (Caki-2/DOX) were constructed, respectively. The expressions of miR-210-3p, ABCC1 and MDR-1 protein were determined by qRT-PCR and Western blot assays. The viability of RCC cells was assessed by MTT assay. The regulatory relationship between miR-210-3p and ABCC1 was analyzed by Dual Luciferase assay. The effect of miR-210-3p in vivo was investigated with a tumor xenograft model in mice.ResultsMiR-210-3p expression was observed to significantly decrease in Caki-2/VBL and Caki-2/DOX cells. Meanwhile, ABCC1 and MDR-1 were significantly increased in Caki-2/VBL and Caki-2/DOX cells. ABCC1 was a novel target of miR-210-3p and negatively regulated by miR-210-3p. And miR-210-3p improved drug-sensitivity of RCC cells. Down-regulation of ABCC1 could reverse the effect of miR-210-3p knockdown on the drug-resistance and the level of MDR-1 in drug-sensitive RCC cells.ConclusionWe confirmed that down-regulation of miR-210-3p increased ABCC1 expression, thereby enhancing the MRP-1-mediated multidrug resistance of RCC cells.
Highlights
ATP-binding cassette transporter super-family including ABCC1 and MDR-1 were involved in multidrug resistance (MDR) of renal cell carcinoma (RCC) patients
The expression of miR‐210‐3p was decreased and the levels of ASCC1 and MDR‐1 were increased in drug‐resistant RCC cells The RCC cell line Caki-2 with vinblastine-resistant (Caki-2/VBL) or doxorubicin-resistant (Caki-2/DOX) were constructed, respectively
The results of quantitative real-time PCR (qRT-PCR) and Western blot assays showed that the expression of miR-210-3p was decreased and the levels of ABCC1 and MDR-1 were increased in Caki-2/DOX and Caki-2/VBL cells, compared to the RCC cell line Caki-2
Summary
ATP-binding cassette transporter super-family including ABCC1 and MDR-1 were involved in multidrug resistance (MDR) of renal cell carcinoma (RCC) patients. The surgical therapy, including radical resection or nephron-sparing surgery, was commonly used as the preferred method for RCC. For those with advanced or recurring RCC patients, chemotherapy is the mainstream method for RCC in clinic, but it has unsatisfactory results in RCC patients [2]. ABCC1 and MDR-1, two numbers of ATP-binding cassette transporter super-family related to multi-drug resistance, were documented to increase in RCC patients and served as the efflux pumps to promote chemotherapeutic drugs out of cancer cells via the assistance of ATPase activity [5, 6]. The expression of ABCC1 and MDR-1 could act as the MDR markers in RCC [6]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
