The microRNA signature of patients with sunitinib failure: regulation of UHRF1 pathways by microRNA-101 in renal cell carcinoma
نویسندگان
چکیده
Molecular targeted therapy is a standard treatment for patients with advanced renal cell carcinoma (RCC). Sunitinib is one of the most common molecular-targeted drugs for metastatic RCC. Molecular mechanisms of sunitinib resistance in RCC cells is still ambiguous. The microRNA (miRNA) expression signature of patients with sunitinib failure in RCC was constructed using a polymerase chain reaction (PCR)-based array. Several miRNAs that were aberrantly expressed in RCC tissues from patients treated with sunitinib were identified in this analysis. MicroRNA-101 (miR- 101) was markedly suppressed in sunitinib treated RCC tissues. Restoration of miR-101 significantly inhibited cell migration and invasion in Caki-1 and 786-O cells. Ubiquitin-like with PHD and ring finger domains 1 (UHRF1) was directly suppressed by miR-101 in RCC cells, and overexpression of UHRF1 was confirmed in sunitinib-treated RCC tissues. The pathways of nucleotide excision repair and mismatch repair were significantly suppressed by knockdown of UHRF1. Our findings showed that antitumor miR-101- mediated UHRF1 pathways may be suppressed by sunitinib treatment.
منابع مشابه
microRNA-29a functions as a tumor suppressor in nasopharyngeal carcinoma 5-8F cells through targeting VEGF
Objective(s): microRNA-29 (miR-29) family miRNAs have been mentioned as tumor suppressive genes in several human cancers. The purpose of this study was to investigate the function of miR-29a in nasopharyngeal carcinoma (NPC) cells. Materials and Methods: Human NPC cell line 5-8F was transfected with mimic, inhibitor or scrambled controls...
متن کاملMicroRNA-205 inhibits renal cells apoptosis via targeting CMTM4
Objective(s):MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate gene expression. They have important roles in kidney development, homeostasis and disease, and participate in the onset and progression of tubulointerstitial sclerosis and end-stage glomerular lesions that occur in various forms of chronic kidney disease (CKD). In the present study, we elucidated the role of microR...
متن کاملRegulation of UHRF1 by microRNA-9 modulates colorectal cancer cell proliferation and apoptosis
The UHRF1 protein is pivotal for DNA methylation and heterochromatin formation, leading to decreased expressions of tumor suppressor genes and contributing to tumorigenesis. However, the factors that modulate UHRF1 expression in colorectal cancer (CRC) remain unclear. Here we showed that, compared with corresponding normal tissues, UHRF1 was upregulated and microRNA-9 (miR-9) was downregulated ...
متن کاملDown-regulation of microRNA-23b aggravates LPS-induced inflammatory injury in chondrogenic ATDC5 cells by targeting PDCD4
Objective(s): Osteoarthritis (OA), characterized by degradation of articular cartilage, is a leading cause of disability. As the only cell type present in cartilage, chondrocytes play curial roles in the progression of OA. In our study, we aimed to explore the roles of miR-23b in the lipopolysaccharide (LPS)-induced inflammatory injury. Materials and Methods: LPS-induced cell injury of ATDC5 ce...
متن کاملThe Role of microRNA in Cancer Cachexia and Muscle Wasting: A Review Article
Almost half of cancer patients experience cachexia syndrome. Cachexic patients are at risk of increased side effects of chemotherapy, reduced tolerance to chemotherapy drugs, longer duration of treatment period, and decreased quality of life. Cancer cachexia is a multifactorial syndrome. Micro ribonucleic acid (miRNA), a “non-coding RNA”, is considered to be a risk factor of cachexia and muscle...
متن کامل