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The Role of Mir-218 in Breast Cancer Bone Metastasis
Başlık:
The Role of Mir-218 in Breast Cancer Bone Metastasis
Yazar:
Liu, Xuxiang, author.
ISBN:
9780438056374
Yazar Ek Girişi:
Fiziksel Tanımlama:
1 electronic resource (116 pages)
Genel Not:
Source: Dissertation Abstracts International, Volume: 79-10(E), Section: B.
Advisors: Emily Wang; John Chan Committee members: Ching-cheng Chen; Marcin Kortylewski; Vu Ngo; Li Zhong.
Özet:
Bone metastasis affects about 70% of late-stage breast cancer patients. Once breast cancer metastasizes to bone, it is incurable. The bone-tropism of breast cancer is attributed to the expression of plasma membrane-bound proteins which facilitate the binding to bone-residing cells or proteins that are enriched in the bone microenvironment. To promote growth in bone, breast cancer cells secrete cytokines to induce osteolysis, which in turn releases growth factors from the bone matrix to nourish cancer cells. Current therapeutic drugs mainly focus on the inhibition of this vicious cycle, but only have palliative effects. During normal bone remodeling, bone resorption is coupled with bone formation. Therefore, the regulation of osteoblast-mediated bone formation is essential for bone homeostasis. On the other hand, microRNAs are important posttranscriptional regulators that have been recently found to mediate cellular crosstalk by secretion through extracellular vesicles. In this study, I find that miR-218 secreted by breast cancer cells directly targets and downregulates type I collagen in osteoblasts, which could potentially facilitate the growth of cancer cells in bone. High expression of miR-218 in breast cancer cells increases the secretion of inhibin ?B which promotes the expression of TIMP3 in osteoblasts, thereby repressing type I collagen processing during bone formation. It would be of value to investigate the possible clinical application of miR-218 as a therapeutic target and diagnostic/prognostic marker for breast cancer bone metastasis. I also examine the possible upstream regulators of miR-218 as well as other microRNAs that may represent other mechanisms through which breast cancer employs to enhance bone metastasis. Moreover, some proteins secreted into the extracellular vesicles by bone-tropic breast cancer cells are identified to potentially mediate the bone cell-tropism of these vesicles.
Notlar:
School code: 0517
Mevcut:*
Yer Numarası | Demirbaş Numarası | Shelf Location | Lokasyon / Statüsü / İade Tarihi |
---|---|---|---|
XX(682799.1) | 682799-1001 | Proquest E-Tez Koleksiyonu | Arıyor... |
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