Decreased miR‐200a‐3p is a key regulator of renal carcinoma growth and migration by directly targeting CBL

Abstract

Although emerging evidence has revealed that microRNAs (miRNAs) dysregulation contribute to carcinogenesis, the mechanism underlying their roles in renal cell carcinoma (RCC) is unclear. The purpose of the current study was to analyze the association of miR-200a-3p expression with RCC and to understand potential novel target genes, functions and mechanisms of miR-200a-3p in RCC. MiR-200a-3p expression levels were first measured by quantitative real-time polymerase chain reaction and in situ hybridization in pairs of RCC tissue samples. Next, the potential miR-200a-3p target gene was analyzed using a combination of computer-aided algorithms, luciferase reporter assays and Western blot analysis. Finally, the biological roles of miR-200a-3p in RCC tumorigenesis were investigated both in vitro by 5-ethynyl-20-deoxyuridine, apoptosis assay and transwell assay, as well as in vivo using a xenograft mouse model. Our results demonstrated that miR-200a-3p was remarkably downregulated in RCC tissues compared with normal adjacent tissue, and CBL is a direct target of miR-200a-3p. An inverse correlation between miR-200a-3p and CBL was observed in RCC tissue samples. Mechanistic investigations revealed that ectopic expression of miR-200a-3p in RCC cell lines suppressed cell proliferation and migration and enforced cell apoptosis by directly inhibiting CBL in vitro and in vivo, whereas silencing miR-200a-3p resulted in the opposite effects. Additionally, overexpressing CBL abolished the effects induced by miR-200a-3p overexpression. Taken together, our results show that the miR-200a-3p/CBL regulation axis is a novel mechanism underlying RCC pathogenesis and may serve as a candidate biomarker and therapeutic target in RCC.

Exosomes Mediated Transfer of Circ_UBE2D2 Enhances the Resistance of Breast Cancer to Tamoxifen by Binding to MiR-200a-3p

“…MicroRNAs (miRNA) have been investigated to participate in the pathological process of many diseases by regulating cell metabolism, proliferation, migration, apoptosis, and drug resistance [ 26 , 27 ]. MiR-200a-3p is a functional miRNA and has been demonstrated to inhibit cell tumorigenesis in many types of cancers, such as papillary thyroid carcinoma [ 28 ], gastric cancer [ 29 ], renal cancer [ 30 ], and so on. In addition, miR-200a-3p also was implied to involve in the regulation of drug resistance.…”

MicroRNA Profiling Reveals an Abundant miR-200a-3p Promotes Skeletal Muscle Satellite Cell Development by Targeting TGF-β2 and Regulating the TGF-β2/SMAD Signaling Pathway

“…In gastric cancer (GC) tissues, miR-200a-3p plays a cancer suppressing role in GC by targeting KLF12 [26]. In renal cell carcinoma (RCC), the miR-200a-3p/CBL regulatory axis is a new mechanism under pathogenesis [27]. After using high-throughput sequencing to analyze the ovarian tissues of chickens with lower and higher egg rates, Wu et al found that miR-200a-3p may play a special central role in the reproductive regulation [28].…”

Mutational Landscape of the BAP1 Locus Reveals an Intrinsic Control to Regulate the miRNA Network and the Binding of Protein Complexes in Uveal Melanoma

“…Among them, the miR-125 family, which potentially acts as tumor suppressors has been reported in different types of cancer, including cutaneous melanoma [46,47]. Likewise, miR-200a-3p (renal carcinoma, pancreatic cancer), miR-423-5p (gastric cancer), miR-31-5p(Oral Cancer), miR-141-3p (rectal cancer) and miR-140-3p.1 (breast cancer) have also been implicated in different types of cancer [48,49,50,51,52,53]. Based on our study, we have observed that the regulatory network associated with BAP1-miRNAs is unique in comparison to the common miRNAs regulatory network in UM.…”