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

Hu, Ke; Liu, Xianhao; Li, Yang; Li, Qinyang; Xu, Yu; Zeng, Wei; Zhong, Guangming; Chen, Yú

doi:10.12659/msm.922253

Cited by 54 publications

(47 citation statements)

References 33 publications

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“… 33 Moreover, Hu et al found that exosome-derived circ_UBE2D2 promoted resistance of breast cancer to tamoxifen via regulating miR-200a-3p. 34 Circ-XIAP has been found to be upregulated and promoted proliferation and migration in PCa. 20 However, the roles of exosomal circ-XIAP in DTX resistance of PCa have not been reported.…”

Section: Discussionmentioning

confidence: 99%

Exosomal Circ-XIAP Promotes Docetaxel Resistance in Prostate Cancer by Regulating miR-1182/TPD52 Axis

Zhang

et al. 2021

DDDT

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Background Exosomal circular RNAs (circRNAs) are involved in the pathogenesis of prostate cancer (PCa) and chemotherapy resistance. This research aimed to explore the function and molecular mechanism of circRNA X-linked inhibitor of apoptosis (circ-XIAP) in docetaxel (DTX) resistance of PCa. Methods The expression of circ-XIAP, microRNA-1182 (miR-1182), tumor protein D52 (TPD52) was measured by quantitative real-time polymerase chain reaction (qRT-PCR). Exosomes were detected with transmission electron microscopy (TEM). Cluster of differentiation 63 (CD63), cluster of differentiation 9 (CD9) and TPD52 protein levels were detected by Western blot (WB). FIfty percent inhibitory concentration (IC50) of DTX and cell viability were determined using Cell Counting Kit-8 (CCK-8) assay. Colony formation assay was applied to assess colony-forming ability. Cell cycle distribution and apoptosis were analyzed by flow cytometry. Transwell assay was used for measuring cell migration and invasion. Dual-reporter luciferase assay was performed to confirm the interaction between miR-1182 and circ-XIAP or TPD52. The role of circ-XIAP in vivo was confirmed via the mice xenograft model. Results Circ-XIAP and TPD52 were upregulated and miR-1182 was downregulated in DTX-resistant PCa tissue specimens and cell lines. Circ-XIAP was also overexpressed in exosomes from DTX-resistant cells and could be transmitted via exosomes. Circ-XIAP knockdown enhanced DTX sensitivity by suppressing DTX-resistant cell proliferation, migration and invasion and inducing cell cycle arrest and apoptosis. Circ-XIAP directly targeted miR-1182, and the effects of circ-XIAP knockdown were reversed by downregulating miR-1182 in DTX-resistant cells. TPD52 was the target of miR-1182, and its upregulation weakened the promotive effect of miR-1182 on DTX sensitivity. Importantly, circ-XIAP depletion inhibited tumor growth and increased DTX sensitivity in vivo. Conclusion Exosomal circ-XIAP promoted DTX resistance of PCa by regulating miR-1182/TPD52 axis, providing a promising therapeutic target for PCa chemotherapy.

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Section: Discussionmentioning

confidence: 99%

Exosomal Circ-XIAP Promotes Docetaxel Resistance in Prostate Cancer by Regulating miR-1182/TPD52 Axis

Zhang

et al. 2021

DDDT

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“…Besides, exosomes have attracted wide attention for the new means of intracellular communication (25,26). Through selectively packaging, secreting, and transferring ncRNAs between cells, tumor-derived exosomes could participate in the numerous hallmarks of breast cancer, including proliferation, metastasis, and drug resistance (17,27,28). Of note, exosomal circRNAs have been a hot research area for their important role in various human cancers (29)(30)(31).…”

Section: Discussionmentioning

confidence: 99%

“…Eight days after the injection, the mice were administrated with 20 mg/kg lapatinib (the sh-NC + Lapatinib group and the sh-circ-MMP11 + Lapatinib group) or the same amount of PBS (the sh-NC group and the sh-circ-MMP11 group) every three days. Tumor volume was measured at the indicated time points (8,11,14,17,21, and 23 days). Some 23 days after treatments, the tumors were obtained, followed by a photograph, weight, and analysis with RT-qPCR assay.…”

Section: Tumor Xenograft Assaymentioning

confidence: 99%

Circular RNA circ-MMP11 Contributes to Lapatinib Resistance of Breast Cancer Cells by Regulating the miR-153-3p/ANLN Axis

Ren

Yao

et al. 2021

Front. Oncol.

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BackgroundDrug-resistance is a major obstacle to the treatment of breast cancer. Circular RNA (circRNA) circ-MMP11 has been reported to be promoting the progression of breast cancer. This study is designed to explore the role and mechanism of circ-MMP11 in lapatinib resistance in breast cancer.MethodsCirc-MMP11, microRNA-153-3p (miR-153-3p), and Anillin (ANLN) levels were detected by real-time quantitative polymerase chain reaction (RT-qPCR). Cell viability, number of colonies, apoptosis, migration, and invasion were detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT), colony formation, flow cytometry, and transwell assays, respectively. Exosomes were exerted and detected by differential centrifugation and a transmission electron microscope. The protein levels of CD63, CD9, and ANLN were assessed by western blot assay. The binding relationship between miR-153-3p and circ-MMP11 or ANLN was predicted by circinteractome or starbase, and then verified by a dual-luciferase reporter assay and RNA pull-down assay. The biological role of circ-MMP11 on breast cancer tumor growth and drug resistance was detected by the xenograft tumor model in vivo.ResultsCirc-MMP11 and ANLN were highly expressed, and miR-153-3p was decreased in LR breast cancer tissues and cells. Circ-MMP11 could be transported by exosomes. Furthermore, circ-MMP11 knockdown promoted lapatinib sensitivity by repressing cell viability, colony number, migration, invasion, and boosting apoptosis in LR breast cancer cells. Circ-MMP11 deficiency improved the drug sensitivity of breast cancer in vivo. Mechanically, circ-MMP11 could regulate ANLN expression through sponging miR-153-3p.ConclusionCirc-MMP11 could be transferred by exosomes in breast cancer cells. And circ-MMP11 functioned as a sponge of miR-153-3p to regulate ANLN expression, thereby promoting lapatinib resistance in breast cancer cells, providing therapeutic targets for the treatment of breast cancer.

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“…This result confirmed that hsa_circ_0025202 could be a therapeutic target in patients with hormone receptor-positive BC receiving TAM therapy. Additionally, circ_UBE2D2 was upregulated in TAM-resistant BC tissues and cell lines while circ_UBE2D2 deletion mitigated TAM resistance in BC cells (Hu et al, 2020 ). Circ_UBE2D2 was also significantly loaded in resistant cell-derived exosomes and could be transferred to parental cells.…”

Section: Circrnas In Bc Drug Resistancementioning

confidence: 99%

Circular RNAs: Their Role in the Pathogenesis and Orchestration of Breast Cancer

Xiao

Tan

et al. 2021

Front. Cell Dev. Biol.

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As one of the most frequently occurring malignancies in women, breast cancer (BC) is still an enormous threat to women all over the world. The high mortality rates in BC patients are associated with BC recurrence, metastatic progression to distant organs, and therapeutic resistance. Circular RNAs (circRNAs), belonging to the non-coding RNAs (ncRNAs), are connected end to end to form covalently closed single-chain circular molecules. CircRNAs are widely found in different species and a variety of human cells, with the features of diversity, evolutionary conservation, stability, and specificity. CircRNAs are emerging important participators in multiple diseases, including cardiovascular disease, inflammation, and cancer. Recent studies have shown that circRNAs are involved in BC progress by regulating gene expression at the transcriptional or post-transcriptional level via binding to miRNAs then inhibiting their function, suggesting that circRNAs may be potential targets for early diagnosis, treatment, and prognosis of BC. Herein, in this article, we have reviewed and summarized the current studies about the biogenesis, features, and functions of circRNAs. More importantly, we emphatically elucidate the pivotal functions and mechanisms of circRNAs in BC growth, metastasis, diagnosis, and drug resistance. Deciphering the complex networks, especially the circRNA-miRNA target gene axis, will endow huge potentials in developing therapeutic strategies for combating BC.

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

Cited by 54 publications

References 33 publications

Exosomal Circ-XIAP Promotes Docetaxel Resistance in Prostate Cancer by Regulating miR-1182/TPD52 Axis

Exosomal Circ-XIAP Promotes Docetaxel Resistance in Prostate Cancer by Regulating miR-1182/TPD52 Axis

Circular RNA circ-MMP11 Contributes to Lapatinib Resistance of Breast Cancer Cells by Regulating the miR-153-3p/ANLN Axis

Circular RNAs: Their Role in the Pathogenesis and Orchestration of Breast Cancer

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