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      Hippo-YAP/TAZ signaling in breast cancer: Reciprocal regulation of microRNAs and implications in precision medicine


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          Breast cancer is a molecularly heterogeneous disease and the most common female malignancy. In recent years, therapy approaches have evolved to accommodate molecular diversity, with a focus on more biologically based therapies to minimize negative consequences. To regulate cell fate in human breast cells, the Hippo signaling pathway has been associated with the alpha subtype of estrogen receptors. This pathway regulates tissue size, regeneration, and healing, as well as the survival of tissue-specific stem cells, proliferation, and apoptosis in a variety of organs, allowing for cell differentiation. Hippo signaling is mediated by the kinases MST1, MST2, LATS1, and LATS2, as well as the adaptor proteins SAV1 and MOB. These kinases phosphorylate the downstream effectors of the Hippo pathway, yes-associated protein (YAP), and transcriptional coactivator with PDZ-binding motif (TAZ), suppressing the expression of their downstream target genes. The Hippo signaling pathway kinase cascade plays a significant role in all cancers. Understanding the principles of this kinase cascade would prevent the occurrence of breast cancer. In recent years, small noncoding RNAs, or microRNAs, have been implicated in the development of several malignancies, including breast cancer. The interconnections between miRNAs and Hippo signaling pathway core proteins in the breast, on the other hand, remain poorly understood. In this review, we focused on highlighting the Hippo signaling system, its key parts, its importance in breast cancer, and its regulation by miRNAs and other related pathways.

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          Most cited references124

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          Breast Cancer Treatment

          Breast cancer will be diagnosed in 12% of women in the United States over the course of their lifetimes and more than 250 000 new cases of breast cancer were diagnosed in the United States in 2017. This review focuses on current approaches and evolving strategies for local and systemic therapy of breast cancer.
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            Long non-coding RNAs: insights into functions.

            In mammals and other eukaryotes most of the genome is transcribed in a developmentally regulated manner to produce large numbers of long non-coding RNAs (ncRNAs). Here we review the rapidly advancing field of long ncRNAs, describing their conservation, their organization in the genome and their roles in gene regulation. We also consider the medical implications, and the emerging recognition that any transcript, regardless of coding potential, can have an intrinsic function as an RNA.
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              Circulating microRNAs as stable blood-based markers for cancer detection.

              Improved approaches for the detection of common epithelial malignancies are urgently needed to reduce the worldwide morbidity and mortality caused by cancer. MicroRNAs (miRNAs) are small ( approximately 22 nt) regulatory RNAs that are frequently dysregulated in cancer and have shown promise as tissue-based markers for cancer classification and prognostication. We show here that miRNAs are present in human plasma in a remarkably stable form that is protected from endogenous RNase activity. miRNAs originating from human prostate cancer xenografts enter the circulation, are readily measured in plasma, and can robustly distinguish xenografted mice from controls. This concept extends to cancer in humans, where serum levels of miR-141 (a miRNA expressed in prostate cancer) can distinguish patients with prostate cancer from healthy controls. Our results establish the measurement of tumor-derived miRNAs in serum or plasma as an important approach for the blood-based detection of human cancer.

                Author and article information

                Genes Dis
                Genes Dis
                Genes & Diseases
                Chongqing Medical University
                23 March 2023
                March 2024
                23 March 2023
                : 11
                : 2
                : 760-771
                [a ]Student Research Committee, Birjand University of Medical Sciences, Birjand 9717853577, Iran
                [b ]Tabas School of Nursing, Birjand University of Medical Sciences, Birjand 9717853577, Iran
                [c ]Department of Biology, University of Sistan and Baluchestan, Zahedan 9816745785, Iran
                [d ]Cellular and Molecular Research Center, Birjand University of Medical Sciences, Birjand 9717853577, Iran
                Author notes
                © 2023 The Authors. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co., Ltd.

                This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

                : 4 July 2022
                : 9 December 2022
                : 29 January 2023
                Review Article

                breast cancer,hippo signaling,large tumor suppressor kinase 1,micrornas,pdz-binding motif,yes-associated protein


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