Normal and cancerous mammary stem cells evade interferon-induced constraint through the miR-199a–LCOR axis

Celià-Terrassa, Toni; Liu, Daniel Dan; Choudhury, A.; Xiang, Haitao; Wei, Yong; Zamalloa, Jose; Alfaro-Aco, Raymundo; Chakrabarti, Rumela; Jiang, Yi; Koh, Bong Ihn; Smith, Heather; DeCoste, Christina J.; Li, Jun Jing; Shao, Zhi Ming; Kang, Yibin

doi:10.1038/ncb3533

Cited by 88 publications

(80 citation statements)

References 68 publications

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“…We also provided evidence for an important role of miR-199a-3p in promoting the malignant transformation of HPCs into HCSCs, which was in agreement with the findings of Alemdehy et al They identified an oncogenic function of miR-199a-3p in acute myeloid leukemia through enhancing proliferation and self-renewal of myeloid progenitors [27]. Celià-Terrassa et al also reported that miR-199a-3p was upregulated in breast CSC populations and induced stem cell-like signatures [55]. Notably, miR-199a-3p was reported to have either tumor-suppressive functions [56,57] or tumor-promoting activities [27,58] across different cancer types, including liver cancer.…”

Section: Discussionsupporting

confidence: 91%

TGF-β1 accelerates the hepatitis B virus X-induced malignant transformation of hepatic progenitor cells by upregulating miR-199a-3p

et al. 2019

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Increasing evidence has suggested that liver cancer arises partially from transformed hepatic progenitor cells (HPCs). However, the detailed mechanisms underlying HPC transformation are poorly understood. In this study, we provide evidence linking the coexistence of hepatitis B virus X protein (HBx) and transforming growth factor beta 1 (TGF-β1) with miR-199a-3p in the malignant transformation of HPCs. The examination of liver cancer specimens demonstrated that HBx and TGF-β1 expression was positively correlated with epithelial cell adhesion molecule (EpCAM) and cluster of differentiation 90 (CD90). Importantly, EpCAM and CD90 expression was much higher in the specimens expressing both high HBx and high TGF-β1 than in those with high HBx or high TGF-β1 and the double-low-expression group. HBx and TGF-β1 double-high expression was significantly associated with poor prognosis in primary liver cancer. We also found that HBx and TGF-β1 induced the transformation of HPCs into hepatic cancer stem cells and promoted epithelial-mesenchymal transformation, which was further enhanced by concomitant HBx and TGF-β1 exposure. Moreover, activation of the c-Jun N-terminal kinase (JNK)/c-Jun pathway was involved in the malignant transformation of HPCs. miR-199a-3p was identified as a significantly upregulated microRNA in HPCs upon HBx and TGF-β1 exposure, which were shown to promote miR-199a-3p expression via c-Jun-mediated activation. Finally, we found that miR-199a-3p was responsible for the malignant transformation of HPCs. In conclusion, our results provide evidence that TGF-β1 cooperates with HBx to promote the malignant transformation of HPCs through a JNK/c-Jun/miR-199a-3p-dependent pathway. This may open new avenues for therapeutic interventions targeting the malignant transformation of HPCs in treating liver cancer.

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Section: Discussionsupporting

confidence: 91%

TGF-β1 accelerates the hepatitis B virus X-induced malignant transformation of hepatic progenitor cells by upregulating miR-199a-3p

et al. 2019

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“…This could also occur in the metastatic niche, as MSCs are found in multiple distant locations 79,80 . miR-199a is also important for normal and breast cancer stem cell plasticity, protecting CSCs from differentiation and senescence elicited by macrophage-secreted IFN-α and promoting tumour initiation, both at primary and metastatic sites 81 . The same miRNA also promotes melanoma metastatic colonization by favouring the recruitment of endothelial cells 82 .…”

Section: Series | Review Articlementioning

confidence: 99%

Metastatic niche functions and therapeutic opportunities

2018

Self Cite

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Metastasis is an inefficient process, especially during colonization at a distant organ. This bottleneck underlies the importance of the metastatic niche for seeding and outgrowth of metastases. Here, we classify the common functions of different metastatic niches: anchorage, survival support, protection from external insults, licensing proliferation and outgrowth. We highlight the emerging role of the metastatic niche in maintaining cancer stemness and promoting immune evasion, and discuss therapeutic opportunities against the metastatic niche.

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“…Through decades of investigations, thousands of miRNAs have been found in humans and animals, among which a notable proportion of miRNAs are found to be critical in the pathogenesis of various diseases, including cardiovascular diseases [9,10,11,12,13,14]. Moreover, some circulating miRNAs predominantly express in CAD patients [15,16].…”

Section: Introductionmentioning

confidence: 99%

miR-126 in Peripheral Blood Mononuclear Cells Negatively Correlates with Risk and Severity and is Associated with Inflammatory Cytokines as well as Intercellular Adhesion Molecule-1 in Patients with Coronary Artery Disease

Zhang²

2018

Cardiology

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Objectives: The aim of this study was to evaluate the association of miR-126 with risk and severity of coronary artery disease (CAD) as well as its correlation with inflammatory cytokines and endothelial related proteins. Methods: In total, 215 patients suspected of CAD who underwent coronary angiography were enrolled in this case control study and were divided into a CAD group (n = 119) and control group (n = 96). miR-126 relative expression was assessed by real-time polymerase chain reaction. Results: The relative expression of miR-126 decreased in CAD patients compared to controls (p < 0.001), and the receiver operating characteristic curve showed a good diagnostic value of miR-126 for CAD risk with an area under the curve of 0.801 (95% CI 0.740-0.861). Additionally, miR-126 was negatively correlated with high-sensitivity C-reactive protein levels (p < 0.001) and reversely associated with TNF-α (p = 0.008) and IL-6 (p < 0.001) levels, while it was positively correlated with the IL-10 level (p < 0.001). In addition, miR-126 was negatively associated with intercellular adhesion molecule-1 (ICAM-1) levels (p = 0.001), and no association of miR-126 with vascular endothelial growth factor was detected (p = 0.142). Meanwhile, the miR-126 relative level was negatively associated with the Gensini score (p < 0.001). Conclusions: Peripheral blood mononuclear cell miR-126 predicts risk and severity and correlates with inflammatory cytokines as well as ICAM-1 in patients with CAD.

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Normal and cancerous mammary stem cells evade interferon-induced constraint through the miR-199a–LCOR axis

Cited by 88 publications

References 68 publications

TGF-β1 accelerates the hepatitis B virus X-induced malignant transformation of hepatic progenitor cells by upregulating miR-199a-3p

TGF-β1 accelerates the hepatitis B virus X-induced malignant transformation of hepatic progenitor cells by upregulating miR-199a-3p

Metastatic niche functions and therapeutic opportunities

miR-126 in Peripheral Blood Mononuclear Cells Negatively Correlates with Risk and Severity and is Associated with Inflammatory Cytokines as well as Intercellular Adhesion Molecule-1 in Patients with Coronary Artery Disease

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