Has2 natural antisense RNA and Hmga2 promote Has2 expression during TGFβ-induced EMT in breast cancer

Kolliopoulos, Constantinos; Lin, Chun‐Yu; Heldin, Carl‐Henrik; Moustakas, Aristidis; Heldin, Paraskevi

doi:10.1016/j.matbio.2018.09.002

Cited by 46 publications

(46 citation statements)

References 83 publications

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“…HMGA2 involvement in EMT is very well documented in a variety of tumors, and we have discussed some of its involvement in tumor EMT and migration in connection with NCCs [146,147,[150][151][152][153][154][211][212][213][214][215][216][217][218][219]. HMGA2 is also involved in EMT of crystalline epithelial cells in lens fibrosis; this process apparently uses the same pathway of TGFβ-regulated EMT, recruiting SMAD3, HMGA2, and SNAI [220][221][222].…”

Section: Hmga In Emtmentioning

confidence: 98%

HMGA Genes and Proteins in Development and Evolution

Vignali

Marracci

2020

IJMS

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HMGA (high mobility group A) (HMGA1 and HMGA2) are small non-histone proteins that can bind DNA and modify chromatin state, thus modulating the accessibility of regulatory factors to the DNA and contributing to the overall panorama of gene expression tuning. In general, they are abundantly expressed during embryogenesis, but are downregulated in the adult differentiated tissues. In the present review, we summarize some aspects of their role during development, also dealing with relevant studies that have shed light on their functioning in cell biology and with emerging possible involvement of HMGA1 and HMGA2 in evolutionary biology.

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Section: Hmga In Emtmentioning

confidence: 98%

HMGA Genes and Proteins in Development and Evolution

Vignali

Marracci

2020

IJMS

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“…Overexpression of linc-ROR upregulates TGF-β signaling, and then, TGF-β signaling promotes proliferation and invasion of BCSCs (77). Activated Smad and non-Smad through TGF-β signaling pathway leads to the induction hyaluronan synthase 2 (Has2) and Has2 antisense (HAS2-AS) transcripts, high mobility group AT-Hook 2 (Hmga2), and EMT inducing transcription factors such as Snail, Snai1, Hmga2, and fibronectin 1 (78). In addition, induction of Hmga2, Has2-AS, and Has2 are accompanied by activation of Akt and Erk1/2 MAPK signaling.…”

Section: Tgf-β Signaling Pathwaymentioning

confidence: 99%

Mechanistic Pathways of Malignancy in Breast Cancer Stem Cells

Yousefnia

Forootan

et al. 2020

Front. Oncol.

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Breast cancer stem cells (BCSCs) are the minor population of breast cancer (BC) cells that exhibit several phenotypes such as migration, invasion, self-renewal, and chemotherapy as well as radiotherapy resistance. Recently, BCSCs have been more considerable due to their capacity for recurrence of tumors after treatment. Recognition of signaling pathways and molecular mechanisms involved in stemness phenotypes of BCSCs could be effective for discovering novel treatment strategies to target BCSCs. This review introduces BCSC markers, their roles in stemness phenotypes, and the dysregulated signaling pathways involved in BCSCs such as mitogen-activated protein (MAP) kinase, PI3K/Akt/nuclear factor kappa B (NFκB), TGF-β, hedgehog (Hh), Notch, Wnt/β-catenin, and Hippo pathway. In addition, this review presents recently discovered molecular mechanisms implicated in chemotherapy and radiotherapy resistance, migration, metastasis, and angiogenesis of BCSCs. Finally, we reviewed the role of microRNAs (miRNAs) in BCSCs as well as several other therapeutic strategies such as herbal medicine, biological agents, anti-inflammatory drugs, monoclonal antibodies, nanoparticles, and microRNAs, which have been more considerable in the last decades.

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“…Several transcription factors are known to modulate HAS2 in response to growth factors, hormones and cytokines (30). Recently, it has been described that HAS2 antisense 1 (HAS2-AS1), a long-non coding RNA that belongs to the class of natural antisense transcripts, is able to control HAS2 epigenetically (32) and that HAS2-AS1 is able to alter the chromatin structure around the HAS2 promoter inducing HAS2 transcription in vascular smooth muscle cells (33) and tumor cells (34,35).…”

Section: Hyaluronanmentioning

confidence: 99%

Sirtuin 1 reduces hyaluronan synthase 2 expression by inhibiting nuclear translocation of NF-κB and expression of the long-noncoding RNA HAS2–AS1

Caon

Bartolini

Moretto

et al. 2020

Journal of Biological Chemistry

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Hyaluronan (HA) is one of the most prevalent glycosaminoglycans of the vascular extracellular matrix (ECM). Abnormal HA accumulation within blood vessel walls is associated with tissue inflammation and is prominent in most vascular pathological conditions such as atherosclerosis and restenosis. Hyaluronan synthase 2 (HAS2) is the main hyaluronan synthase enzyme involved in HA synthesis and uses cytosolic UDP-glucuronic acid and UDP-GlcNAc as substrates. The synthesis of UDP-glucuronic acid can alter the NAD+/NADH ratio via the enzyme UDP-glucose dehydrogenase, which oxidizes the alcohol group at C6 to the COO− group. Here, we show that HAS2 expression can be modulated by sirtuin 1 (SIRT1), the master metabolic sensor of the cell, belonging to the class of NAD+-dependent deacetylases. Our results revealed the following. 1) Treatments of human aortic smooth muscle cells (AoSMCs) with SIRT1 activators (SRT1720 and resveratrol) inhibit both HAS2 expression and accumulation of pericellular HA coats. 2) Tumor necrosis factor α (TNFα) induced HA-mediated monocyte adhesion and AoSMC migration, whereas SIRT1 activation prevented immune cell recruitment and cell motility by reducing the expression levels of the receptor for HA-mediated motility, RHAMM, and the HA-binding protein TNF-stimulated gene 6 protein (TSG6). 3) SIRT1 activation prevented nuclear translocation of NF-κB (p65), which, in turn, reduced the levels of HAS2–AS1, a long-noncoding RNA that epigenetically controls HAS2 mRNA expression. In conclusion, we demonstrate that both HAS2 expression and HA accumulation by AoSMCs are down-regulated by the metabolic sensor SIRT1.

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Has2 natural antisense RNA and Hmga2 promote Has2 expression during TGFβ-induced EMT in breast cancer

Cited by 46 publications

References 83 publications

HMGA Genes and Proteins in Development and Evolution

HMGA Genes and Proteins in Development and Evolution

Mechanistic Pathways of Malignancy in Breast Cancer Stem Cells

Sirtuin 1 reduces hyaluronan synthase 2 expression by inhibiting nuclear translocation of NF-κB and expression of the long-noncoding RNA HAS2–AS1

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