ZNF281-miR-543 Feedback Loop Regulates Transforming Growth Factor-β-Induced Breast Cancer Metastasis

Ji, Wei; Mu, Qiang; Liu, Xiangyu; Cao, Xuchen; Yu, Yue

doi:10.1016/j.omtn.2020.05.020

Cited by 22 publications

(21 citation statements)

References 41 publications

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“…We found that changes to the motifs of 14 TFs were predictive of expression changes ( Figure 3—figure supplement 2d , Supplementary file 3b ). All of these TFs had a positive correlation between changes in their predicted binding affinity and changes in expression of their bound sequences, reflective of their known capability to promote transcription ( Suske, 2017 ; Frey-Jakobs et al, 2018 ; Bruderer et al, 2013 ; Frietze et al, 2010 ; Song et al, 2003 ; Zhu et al, 2018 ; Ji et al, 2020 ; Morita et al, 2016 ; Syafruddin et al, 2020 ). Of note, the use of an mP with basal activity in the MPRA design means that transcriptional repression is less likely to be detected, and therefore, further investigation is required in order to identify potential repressive activity in these sequences (see Discussion).…”

Section: Resultsmentioning

confidence: 99%

The cis-regulatory effects of modern human-specific variants

Weiss

Harshman

Inoue

et al. 2021

eLife

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The Neanderthal and Denisovan genomes enabled the discovery of sequences that differ between modern and archaic humans, the majority of which are noncoding. However, our understanding of the regulatory consequences of these differences remains limited, in part due to the decay of regulatory marks in ancient samples. Here, we used a massively parallel reporter assay in embryonic stem cells, neural progenitor cells, and bone osteoblasts to investigate the regulatory effects of the 14,042 single-nucleotide modern human-specific variants. Overall, 1791 (13%) of sequences containing these variants showed active regulatory activity, and 407 (23%) of these drove differential expression between human groups. Differentially active sequences were associated with divergent transcription factor binding motifs, and with genes enriched for vocal tract and brain anatomy and function. This work provides insight into the regulatory function of variants that emerged along the modern human lineage and the recent evolution of human gene expression.

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Section: Resultsmentioning

confidence: 99%

The cis-regulatory effects of modern human-specific variants

Weiss

Harshman

Inoue

et al. 2021

eLife

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“…Most of the preclinical mice models (54.4%) were generated by injecting luciferase (Luc)-labeled BC cells transfected with DNA or lentiviral plasmids. In detail, a lentiviral vector was used to modulate the expression of miR-206 [ 95 ], -1 [ 70 ], -124 [ 131 ], -211-5p [ 128 ], -494 [ 78 ], -1204 [ 53 ], -133b [ 48 , 54 ], -101 [ 25 ], -630 [ 90 ], -150 [ 104 ], -133a-3p [ 49 ], -452 [ 62 ], -543 [ 80 ], -96 [ 22 ], -29a [ 55 ], -455-3p [ 77 ], -30a [ 127 ], -100 [ 84 ], -548j [ 86 ], -940 [ 71 ], -429 [ 51 ], -442a [ 88 ], -373 [ 89 ], -509 [ 121 ], -190 [ 79 ], -125b [ 42 , 106 ], -125a-5p [ 72 , 73 ], -33a [ 120 ], -33b [ 23 ], -138 [ 100 ], -27b [ 134 ], -454-3p [ 57 ], -23a [ 87 ] and -218-5p [ 130 ], as well as of miR-30 family members (miR-30a-b-c-d-e) [ 58 ]. A lentiviral vector was also generated to express a circular inhibitor miRNA (CimiRs) specific to silencing the expression of miR-223 and miR-21 [ 118 ].…”

Section: Resultsmentioning

confidence: 99%

“…Lung metastasis was suppressed when BC-luc cells were transfected with the following miRNAs: miR-630 [ 90 ], -452 [ 62 ], -590-3p [ 119 ], -150 [ 104 ], -543 [ 80 ], -133a-3p [ 49 ], -133b [ 48 ] and 14q32 microRNA cluster [ 83 ], or transfected with the inhibitors for miR-106b-5p [ 52 ], -23a [ 87 ] and -454-3p [ 57 ], or when mice were injected with shrimp miR-35 [ 64 ], with a small molecule that binds the precursor of miR-21, activating its destruction [ 94 ]. On the contrary, an increased incidence of metastasis was established in mice injected with BC cells overexpressing miR-29a [ 55 ] and -373 [ 89 ].…”

Section: Resultsmentioning

confidence: 99%

Preclinical Imaging Evaluation of miRNAs’ Delivery and Effects in Breast Cancer Mouse Models: A Systematic Review

Orlandella

Auletta

Greco

et al. 2021

Cancers

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Background: We have conducted a systematic review focusing on the advancements in preclinical molecular imaging to study the delivery and therapeutic efficacy of miRNAs in mouse models of breast cancer. Methods: A systematic review of English articles published in peer-reviewed journals using PubMed, EMBASE, BIOSIS™ and Scopus was performed. Search terms included breast cancer, mouse, mice, microRNA(s) and miRNA(s). Results: From a total of 2073 records, our final data extraction was from 114 manuscripts. The most frequently used murine genetic background was Balb/C (46.7%). The most frequently used model was the IV metastatic model (46.8%), which was obtained via intravenous injection (68.9%) in the tail vein. Bioluminescence was the most used frequently used tool (64%), and was used as a surrogate for tumor growth for efficacy treatment or for the evaluation of tumorigenicity in miRNA-transfected cells (29.9%); for tracking, evaluation of engraftment and for response to therapy in metastatic models (50.6%). Conclusions: This review provides a systematic and focused analysis of all the information available and related to the imaging protocols with which to test miRNA therapy in an in vivo mice model of breast cancer, and has the purpose of providing an important tool to suggest the best preclinical imaging protocol based on available evidence.

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“…By intersecting the miRNA list of GSE113740 (selection criteria: adjusted P < 0.05, |logFC|≥1) and that of GSE146477 (selection criteria: adjusted P < 0.05, |log 2 FC|≥1), miR-543 was identified as the candidate miRNA that may participate in breast cancer pathogenesis ( Figure 1a ). miR-543 was a significant suppressor of breast cancer [ 6 , 24 , 25 ]. Nonetheless, the study of miR-543 in breast cancer is still limited.…”

Section: Resultsmentioning

confidence: 99%

“…Furthermore, miR-543 expression was previously revealed to be significantly decreased in breast cancer tissues, which showed the metastasis-suppressive role of miR-543 in breast cancer. For example, Ji and colleagues demonstrated that miR-543 inhibits the EMT-like phenotype and TGF-β-induced breast cancer metastasis both in vitro and in vivo by targeting ZNF218 [ 24 ]. Wang and et al illustrated that miR-543 inhibited the malignant behavior of triple-negative breast cancer by directly targeting ACTL6A and suppressing ACTL6A expression [ 19 ].…”

Section: Discussionmentioning

confidence: 99%

miR-543 impairs breast cancer cell phenotypes by targeting and suppressing ubiquitin-conjugating enzyme E2T (UBE2T)

2021

Bioengineered

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Breast cancer, with high morbidity worldwide, is a threat to the life of women. MiR-543 was identified as playing an active part in the development of breast cancer involving multiple molecules. The goal of this study was to explore the molecular mechanisms of the involvement of miR-543 in the development of breast cancer. Quantitative real-time PCR (qRT-PCR) or Western blotting was used to detect mRNA or protein expression. Cell counting kit-8 (CCK-8), and the 5-bromo-2ʹ-deoxyuridine (BrdU), wound healing, and Transwell assays were the main experimental procedures. Furthermore, subcutaneous tumor formation experiments were conducted to detect the function of miR-543 in breast cancer development in vivo. The match of miR-543 and ubiquitin-conjugating enzyme E2T (UBE2T) was detected through a dual-luciferase reporter experiment and RNA pull-down assay. Based on these results, miR-543 exhibited reduced expression in breast cancer tissues and cell lines, whereas UBE2T exhibited high levels. Furthermore, miR-543 directly targeted UBE2T, and a negative correlation between miR-543 and UBE2T was also observed in breast cancer tissues. Moreover, miR-543 overexpression led to inhibition of viability, proliferation, migration, and invasion of breast cancer. Furthermore, miR-543 overexpression undermined the UBE2T promotional effect by inhibiting ERK/MAPK pathway activity in breast cancer cells. Our study revealed that miR-543 impaired breast cancer progression by targeting UBE2T and downregulating UBE2T expression through the ERK/MAPK pathway, which suggested that miR-543 and UBE2T might serve as promising therapeutic gene targets for breast cancer in clinical application.

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ZNF281-miR-543 Feedback Loop Regulates Transforming Growth Factor-β-Induced Breast Cancer Metastasis

Cited by 22 publications

References 41 publications

The cis-regulatory effects of modern human-specific variants

The cis-regulatory effects of modern human-specific variants

Preclinical Imaging Evaluation of miRNAs’ Delivery and Effects in Breast Cancer Mouse Models: A Systematic Review

miR-543 impairs breast cancer cell phenotypes by targeting and suppressing ubiquitin-conjugating enzyme E2T (UBE2T)

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