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

Ding, Meng; Sun, Xinlei; Zhong, Jinsha; Zhang, Cuiping; Tian, Yao; Ge, Jingping; Zhang, Chenyu; Zen, Ke; Wang, Jun‐Jun; Wang, Cheng

doi:10.1002/jcb.27326

Cited by 21 publications

(15 citation statements)

References 31 publications

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“…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.…”

Section: Discussionmentioning

confidence: 99%

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

Liu

et al. 2020

Med Sci Monit

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Background Circular RNA UBE2D2 (circ_UBE2D2) has been found to be involved in the progression of breast cancer. Exosomes are critical mediators of intercellular communication, however, the function of exosomal circ_UBE2D2 in breast cancer remains vague. Material/Methods Cell viability was measured by Cell Counting Kit-8 assay. Western blot was used to detect the levels of estrogen receptor alpha (ERα), E-cadherin, vimentin, CD9, and CD63. Migrated and invaded cells were examined using Transwell assay. Circ_UBE2D2 and microRNA (miR)-200a-3p levels were detected using quantitative real-time polymerase chain reaction. Exosomes were isolated by ultracentrifugation method. The interaction between circ_UBE2D2 and miR-200a-3p was confirmed by dual-luciferase reporter assay and RNA immunoprecipitation assay. Murine xenograft model was established to conduct in vivo experiments. Results We found that circ_UBE2D2 was upregulated in breast cancer tamoxifen-resistant tissues and cell lines, and circ_UBE2D2 deletion mitigated tamoxifen resistance in breast cancer cells. Circ_UBE2D2 was also significantly loaded in exosomes isolated from resistant cells and could be transferred to parental cells. MiR-200a-3p was a target of circ_UBE2D2, and we demonstrated that exosomes mediated transfer of circ_UBE2D2 interacted with miR-200a-3p to enhance tamoxifen resistance of breast cancer cells by regulating cell viability, metastasis, and the level of ERα in vivo and in vitro . Conclusions Exosomes mediated transfer of circ_UBE2D2 reinforced tamoxifen resistance in breast cancer by binding to miR-200a-3p, providing new insights into the boost of the effectiveness of tamoxifen on breast cancer patients.

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Section: Discussionmentioning

confidence: 99%

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

Liu

et al. 2020

Med Sci Monit

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“…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].…”

Section: Discussionmentioning

confidence: 99%

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

Yin

Shen

et al. 2020

IJMS

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MicroRNAs (miRNAs) are evolutionarily conserved, small noncoding RNAs that play critical post-transcriptional regulatory roles in skeletal muscle development. Chicken is an optimal model to study skeletal muscle formation because its developmental anatomy is similar to that of mammals. In this study, we identified potential miRNAs in the breast muscle of broilers and layers at embryonic day 10 (E10), E13, E16, and E19. We detected 1836 miRNAs, 233 of which were differentially expressed between broilers and layers. In particular, miRNA-200a-3p was significantly more highly expressed in broilers than layers at three time points. In vitro experiments showed that miR-200a-3p accelerated differentiation and proliferation of chicken skeletal muscle satellite cells (SMSCs) and inhibited SMSCs apoptosis. The transforming growth factor 2 (TGF-β2) was identified as a target gene of miR-200a-3p, and which turned out to inhibit differentiation and proliferation, and promote apoptosis of SMSCs. Exogenous TGF-β2 increased the abundances of phosphorylated SMAD2 and SMAD3 proteins, and a miR-200a-3p mimic weakened this effect. The TGF-β2 inhibitor treatment reduced the promotional and inhibitory effects of miR-200a-3p on SMSC differentiation and apoptosis, respectively. Our results indicate that miRNAs are abundantly expressed during embryonic skeletal muscle development, and that miR-200a-3p promotes SMSC development by targeting TGF-β2 and regulating the TGF-β2/SMAD signaling pathway.

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“…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.…”

Section: Discussionmentioning

confidence: 99%

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

Sharma

Biswas²,

Liu

et al. 2019

Cancers

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The BAP1 (BRCA1-associated protein 1) gene is associated with a variety of human cancers. With its gene product being a nuclear ubiquitin carboxy-terminal hydrolase with deubiquitinase activity, BAP1 acts as a tumor suppressor gene with potential pleiotropic effects in multiple tumor types. Herein, we focused specifically on uveal melanoma (UM) in which BAP1 mutations are associated with a metastasizing phenotype and decreased survival rates. We identified the ubiquitin carboxyl hydrolase (UCH) domain as a major hotspot region for the pathogenic mutations with a high evolutionary action (EA) score. This also includes the mutations at conserved catalytic sites and the ones overlapping with the phosphorylation residues. Computational protein interaction studies revealed that distant BAP1-associated protein complexes (FOXK2, ASXL1, BARD1, BRCA1) could be directly impacted by this mutation paradigm. We also described the conformational transition related to BAP1-BRCA-BARD1 complex, which may pose critical implications for mutations, especially at the docking interfaces of these three proteins. The mutations affect - independent of being somatic or germline - the binding affinity of miRNAs embedded within the BAP1 locus, thereby altering the unique regulatory network. Apart from UM, BAP1 gene expression and survival associations were found to be predictive for the prognosis in several (n = 29) other cancer types. Herein, we suggest that although BAP1 is conceptually a driver gene in UM, it might contribute through its interaction partners and its regulatory miRNA network to various aspects of cancer. Taken together, these findings will pave the way to evaluate BAP1 in a variety of other human cancers with a shared mutational spectrum.

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

Cited by 21 publications

References 31 publications

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

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

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

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

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