scholarly journals TARBP2 Suppresses Ubiquitin-Proteasomal Degradation of HIF-1α in Breast Cancer

2021 ◽  
Vol 23 (1) ◽  
pp. 208
Author(s):  
Jie-Ning Li ◽  
Pai-Sheng Chen ◽  
Ching-Feng Chiu ◽  
Yu-Jhen Lyu ◽  
Chiao Lo ◽  
...  

TAR (HIV-1) RNA binding protein 2 (TARBP2) is an RNA-binding protein participating in cytoplasmic microRNA processing. Emerging evidence has shown the oncogenic role of TARBP2 in promoting cancer progression, making it an unfavorable prognosis marker for breast cancer. Hypoxia is a hallmark of the tumor microenvironment which induces hypoxia-inducible factor-1α (HIF-1α) for transcriptional regulation. HIF-1α is prone to be rapidly destabilized by the ubiquitination–proteasomal degradation system. In this study, we found that TARBP2 expression is significantly correlated with induced hypoxia signatures in human breast cancer tissues. At a cellular level, HIF-1α protein level was maintained by TARBP2 under either normoxia or hypoxia. Mechanistically, TARBP2 enhanced HIF-1α protein stability through preventing its proteasomal degradation. In addition, downregulation of multiple E3 ligases targeting HIF-1α (VHL, FBXW7, TRAF6) and reduced ubiquitination of HIF-1α were also induced by TARBP2. In support of our clinical findings that TARBP2 is correlated with tumor hypoxia, our IHC staining showed the positive correlation between HIF-1α and TARBP2 in human breast cancer tissues. Taken together, this study indicates the regulatory role of TARBP2 in the ubiquitination–proteasomal degradation of HIF-1α protein in breast cancer.

Oncogene ◽  
2019 ◽  
Vol 38 (45) ◽  
pp. 7106-7112 ◽  
Author(s):  
Laia Piqué ◽  
Alexia Martinez de Paz ◽  
David Piñeyro ◽  
Anna Martínez-Cardús ◽  
Manuel Castro de Moura ◽  
...  

1994 ◽  
Vol 269 (16) ◽  
pp. 12285-12289
Author(s):  
F.H. Sarkar ◽  
M.R. Smith ◽  
T. Hoover ◽  
G. Princler ◽  
J.D. Crissman ◽  
...  

2016 ◽  
Author(s):  
Jiwoo Lee ◽  
Han Suk Ryu ◽  
Bok Sil Hong ◽  
Han-Byoel Lee ◽  
Minju Lee ◽  
...  

ABSTRACTSIntroductionThe role of adipocytes in cancer microenvironment has gained focus during the recent years. However, the characteristics of the cancer-associated adipocytes (CAA) in human breast cancer tissues and the underlying regulatory mechanism are not clearly understood.MethodWe reviewed pathology specimens of breast cancer patients to understand the morphologic characteristics of CAA, and profiled the mRNA and miRNA expression of CAA by using indirect co-culture system in vitro.ResultsThe CAAs in human breast cancers showed heterogeneous topographic relationship with breast cancer cells within the breast microenvironment. The CAAs exhibited the characteristics of de-differentiation determined by their microscopic appearance and the expression levels of adipogenic markers. Additionally, the 3T3-L1 adipocytes co-cultured with breast cancer cells showed up-regulation of inflammation-related genes including Il6 and Ptx3. The up-regulation of IL6 in CAA was further observed in human breast cancer tissues. miRNA array of co-cultured 3T3-L1 cells showed increased expression of mmu-miR-5112 which may target Cpeb1. Cpeb1 is a negative regulator of Il6. The suppressive role of mmu-miR-5112 was confirmed by dual luciferase reporter assay, and mmu-miR-5112-treated adipocytes showed up-regulation of Il6. The transition of adipocytes into more inflammatory CAA resulted in proliferation-promoting effect in ER positive breast cancer cells such as MCF7 and ZR-75-1 but not in ER negative cells.ConclusionIn this study, we have determined the de-differentiated and inflammatory natures of CAA in breast cancer microenvironment. Additionally, we propose a miRNA-based regulatory mechanism underlying the process of acquiring inflammatory phenotypes in CAA.


2011 ◽  
Author(s):  
Patsharaporn Techasintana ◽  
Matthew Michael Gubin ◽  
Joseph David Magee ◽  
Garrett MacKenzie Dahm ◽  
Ulus Atasoy

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Zahraa I. Khamis ◽  
Ziad J. Sahab ◽  
Stephen W. Byers ◽  
Qing-Xiang Amy Sang

Research efforts were focused on genetic alterations in epithelial cancer cells. Epithelial-stromal interactions play a crucial role in cancer initiation, progression, invasion, angiogenesis, and metastasis; however, the active role of stroma in human breast tumorigenesis in relation to estrogen receptor (ER) status of epithelial cells has not been explored. Using proteomics and biochemical approaches, we identified two stromal proteins in ER-positive and ER-negative human breast cancer tissues that may affect malignant transformation in breast cancer. Two putative biomarkers, T-cell receptor alpha (TCR-α) and zinc finger and BRCA1-interacting protein with a KRAB domain (ZBRK1), were detected in leukocytes of ER-positive and endothelial cells of ER-negative tissues, respectively. Our data suggest an immunosuppressive role of leukocytes in invasive breast tumors, propose a multifunctional nature of ZBRK1 in estrogen receptor regulation and angiogenesis, and demonstrate the aggressiveness of ER-negative human breast carcinomas. This research project may identify new stromal drug targets for the treatment of breast cancer patients.


Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2658
Author(s):  
Monica Marro ◽  
Anna Maria Rodríguez-Rivero ◽  
Cuauhtémoc Araujo-Andrade ◽  
Maria Teresa Fernández-Figueras ◽  
Laia Pérez-Roca ◽  
...  

Microcalcifications are detected through mammography screening and, depending on their morphology and distribution (BI-RADS classification), they can be considered one of the first indicators of suspicious cancer lesions. However, the formation of hydroxyapatite (HAp) calcifications and their relationship with malignancy remains unknown. In this work, we report the most detailed three-dimensional biochemical analysis of breast cancer microcalcifications to date, combining 3D Raman spectroscopy imaging and advanced multivariate analysis in order to investigate in depth the molecular composition of HAp calcifications found in 26 breast cancer tissue biopsies. We demonstrate that DNA has been naturally adsorbed and encapsulated inside HAp microcalcifications. Furthermore, we also show the encapsulation of other relevant biomolecules in HAp calcifications, such as lipids, proteins, cytochrome C and polysaccharides. The demonstration of natural DNA biomineralization, particularly in the tumor microenvironment, represents an unprecedented advance in the field, as it can pave the way to understanding the role of HAp in malignant tissues.


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