YWHAZ interacts with DAAM1 to promote cell migration in breast cancer

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Abstract

Dishevelled-associated activator of morphogenesis 1 (DAAM1) is a critical driver in facilitating metastasis in breast cancer (BrCa). However, molecular mechanisms for the regulation of DAAM1 activation are only partially elucidated. In this research, the expression levels of YWHAZ and DAAM1 were examined by immunohistochemistry (IHC) staining in BrCa tissues. The functional roles of tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta (YWHAZ)–DAAM1 axis and their regulator microRNA-613 (miR-613) in BrCa cells and associated molecular mechanisms were demonstrated in vitro. As results, the expression levels of DAAM1 and YWHAZ were significantly upregulated in BrCa tissues compared with normal tissues and remarkably associated with poor prognosis. Besides, DAAM1 and YWHAZ were positively correlated with each other in BrCa tissues. YWHAZ interacted and colocalized with DAAM1 in BrCa cells, which was essential for DAAM1-mediated microfilament remodeling and RhoA activation. Moreover, miR-613 directly targeted both YWHAZ and DAAM1, contributing to inhibiting BrCa cells migration via blocking the complex of YWHAZ–DAAM1. To sum up, these data reveal that YWHAZ regulates DAAM1 activation, and the YWHAZ–DAAM1 complex is directly targeted by the shared post-transcriptional regulator miR-613.

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Most cited references 47

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Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries

Hyuna Sung, Jacques Ferlay, Rebecca Siegel … (2021)

This article provides an update on the global cancer burden using the GLOBOCAN 2020 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer. Worldwide, an estimated 19.3 million new cancer cases (18.1 million excluding nonmelanoma skin cancer) and almost 10.0 million cancer deaths (9.9 million excluding nonmelanoma skin cancer) occurred in 2020. Female breast cancer has surpassed lung cancer as the most commonly diagnosed cancer, with an estimated 2.3 million new cases (11.7%), followed by lung (11.4%), colorectal (10.0 %), prostate (7.3%), and stomach (5.6%) cancers. Lung cancer remained the leading cause of cancer death, with an estimated 1.8 million deaths (18%), followed by colorectal (9.4%), liver (8.3%), stomach (7.7%), and female breast (6.9%) cancers. Overall incidence was from 2-fold to 3-fold higher in transitioned versus transitioning countries for both sexes, whereas mortality varied <2-fold for men and little for women. Death rates for female breast and cervical cancers, however, were considerably higher in transitioning versus transitioned countries (15.0 vs 12.8 per 100,000 and 12.4 vs 5.2 per 100,000, respectively). The global cancer burden is expected to be 28.4 million cases in 2040, a 47% rise from 2020, with a larger increase in transitioning (64% to 95%) versus transitioned (32% to 56%) countries due to demographic changes, although this may be further exacerbated by increasing risk factors associated with globalization and a growing economy. Efforts to build a sustainable infrastructure for the dissemination of cancer prevention measures and provision of cancer care in transitioning countries is critical for global cancer control.

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Predicting effective microRNA target sites in mammalian mRNAs

Vikram Agarwal, George Bell, Jin-Wu Nam … (2015)

MicroRNA targets are often recognized through pairing between the miRNA seed region and complementary sites within target mRNAs, but not all of these canonical sites are equally effective, and both computational and in vivo UV-crosslinking approaches suggest that many mRNAs are targeted through non-canonical interactions. Here, we show that recently reported non-canonical sites do not mediate repression despite binding the miRNA, which indicates that the vast majority of functional sites are canonical. Accordingly, we developed an improved quantitative model of canonical targeting, using a compendium of experimental datasets that we pre-processed to minimize confounding biases. This model, which considers site type and another 14 features to predict the most effectively targeted mRNAs, performed significantly better than existing models and was as informative as the best high-throughput in vivo crosslinking approaches. It drives the latest version of TargetScan (v7.0; targetscan.org), thereby providing a valuable resource for placing miRNAs into gene-regulatory networks. DOI: http://dx.doi.org/10.7554/eLife.05005.001

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miRDB: an online database for prediction of functional microRNA targets

Yuhao Chen, Xiaowei Wang (2019)

Abstract MicroRNAs (miRNAs) are small noncoding RNAs that act as master regulators in many biological processes. miRNAs function mainly by downregulating the expression of their gene targets. Thus, accurate prediction of miRNA targets is critical for characterization of miRNA functions. To this end, we have developed an online database, miRDB, for miRNA target prediction and functional annotations. Recently, we have performed major updates for miRDB. Specifically, by employing an improved algorithm for miRNA target prediction, we now present updated transcriptome-wide target prediction data in miRDB, including 3.5 million predicted targets regulated by 7000 miRNAs in five species. Further, we have implemented the new prediction algorithm into a web server, allowing custom target prediction with user-provided sequences. Another new database feature is the prediction of cell-specific miRNA targets. miRDB now hosts the expression profiles of over 1000 cell lines and presents target prediction data that are tailored for specific cell models. At last, a new web query interface has been added to miRDB for prediction of miRNA functions by integrative analysis of target prediction and Gene Ontology data. All data in miRDB are freely accessible at http://mirdb.org.

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Author and article information

Contributors

Yan Zhang:

ORCID: http://orcid.org/0000-0002-7983-8396

fuyou2007@126.com

Yichao Zhu:

ORCID: http://orcid.org/0000-0003-3499-8510

zhuyichao@njmu.edu.cn

Journal

Journal ID (nlm-ta): Cell Death Discov

Journal ID (iso-abbrev): Cell Death Discov

Title: Cell Death Discovery

Publisher: Nature Publishing Group UK (London )

ISSN (Electronic): 2058-7716

Publication date (Electronic): 27 August 2021

Publication date PMC-release: 27 August 2021

Publication date Collection: 2021

Volume: 7

Electronic Location Identifier: 221

Affiliations

[1 ]GRID grid.89957.3a, ISNI 0000 0000 9255 8984, Department of Oncology, , Wuxi Maternal and Child Health Hospital Affiliated to Nanjing Medical University, ; Wuxi, 214023 China

[2 ]GRID grid.89957.3a, ISNI 0000 0000 9255 8984, Wuxi College of Clinical Medicine, , Nanjing Medical University, ; Wuxi, 214023 China

[3 ]GRID grid.89957.3a, ISNI 0000 0000 9255 8984, Department of Physiology, , Nanjing Medical University, ; Nanjing, 211166 China

[4 ]GRID grid.89957.3a, ISNI 0000 0000 9255 8984, Department of Breast Surgery, , Wuxi Maternal and Child Health Hospital Affiliated to Nanjing Medical University, ; Wuxi, 214023 China

[5 ]GRID grid.460176.2, ISNI 0000 0004 1775 8598, Department of Gastroenterology, , Wuxi People’s Hospital Affiliated to Nanjing Medical University, ; Wuxi, 214023 China

[6 ]GRID grid.89957.3a, ISNI 0000 0000 9255 8984, State Key Laboratory of Reproductive Medicine, , Nanjing Medical University, ; Nanjing, 211166 China

Author information

Yan Zhang http://orcid.org/0000-0002-7983-8396

Yichao Zhu http://orcid.org/0000-0003-3499-8510

Article

Publisher ID: 609

DOI: 10.1038/s41420-021-00609-7

PMC ID: 8397740

PubMed ID: 34453038

SO-VID: 1b07817e-cc90-4212-b750-3e96cca51084

License:

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

History

Date received : 25 April 2021

Date revision received : 6 August 2021

Date accepted : 18 August 2021

Funding

Funded by: FundRef https://doi.org/10.13039/501100008109, Wuxi Municipal Bureau on Science and Technology (Wuxi Science and Technology Bureau);

Award ID: N20201006

Award Recipient : Yan Zhang

Funded by: Wuxi Double-Hundred Talent Fund Project (BJ2020076)

Funded by: Jiangsu Postgraduate Training Innovation Project (KYCX21-1559)

Funded by: High-end Medical Expert Team of the 2020 Taihu Talent Plan

Funded by: FundRef https://doi.org/10.13039/501100001809, National Natural Science Foundation of China (National Science Foundation of China);

Award ID: 82073194

Award Recipient : Yichao Zhu

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Keywords: breast cancer,metastasis

Data availability:

Keywords: breast cancer, metastasis

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YWHAZ interacts with DAAM1 to promote cell migration in breast cancer

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Karger: Oncology

Most cited references 47

Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries

Predicting effective microRNA target sites in mammalian mRNAs

miRDB: an online database for prediction of functional microRNA targets

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