HDAC9 overexpression confers invasive and angiogenic potential to triple negative breast cancer cells via modulating microRNA-206

Salgado, Eric; Bian, Xu-ming; Feng, Amber; Shim, Hyunsuk; Liang, Zhongxing

doi:10.1016/j.bbrc.2018.06.120

Cited by 37 publications

(32 citation statements)

References 44 publications

(41 reference statements)

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“…The fact that the expression of miR-206 was significantly down-regulated in TNBC compared to non-TNBC strongly suggested its involvement in the development of more aggressive characteristics associated with TNBC subtype. These findings are in accordance with results of Salgadoa et al who also reported that TNBC tissues and cell lines expressed miR-206 less than non-TNBC equivalents [23]. Downregulation of miR-206 in TNBC have been linked with repression of cell migration via direct targeting of many proteins including actin-binding protein coronin 1C [24].…”

Section: Discussionsupporting

confidence: 92%

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VEGF and KRAS are Potential Targets of miR-206 Modulation in Triple Negative Breast Cancer

Feky¹,

Ibrahim²,

Nassar³

et al. 2019

JCRT

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Triple negative is a subtype of breast cancer characterized by lack of expression of hormone receptors (ER, PR and Her2/neu). Due to the limited treatment options, the search for novel treatment targets continues. The aim of this study was to assess the differential expression of miR-206, VEGF and KRAS in TNBC and non-TNBC tissues and cell lines and to evaluate the modulatory effect of miR-206 on the key oncogenic targets VEGF and KRAS. The expression of miR-206, VEGF and KRAS was quantified using real time PCR in both paraffin embedded breast cancer and adjacent tissues as well as in MDA-MB-231 and MCF-7 cell lines. Cell lines were transfected with different concentrations of miR-206 mimic and their viability were assessed using MTT assay. Our results indicated that miR-206 was significantly downregulated in cancerous compared to non-cancerous tissues with a more pronounced downregulation in TNBC than non-TNBC tissues. VEGF and KRAS were significantly upregulated in TNBC compared to non-TNBC and their expression was negatively correlated to miR-206 expression. Transfection of TNBC and non-TNBC cell lines with miR-206 mimic resulted in a dose dependent reduction in cell viability as well as a significant reduction in VEGF and KRAS expression. In conclusion, based on our combined human tissues and cell line-based investigations we can suggest that VEGF and KRAS may be potential targets for miR-206-mediated regulation and that their targeting by miR-206 can be a highly efficient therapeutic strategy in TNBC.

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Section: Discussionsupporting

confidence: 92%

“…Previous reports have supported the role of miR-206 in the progression of many types of cancers [21]. Low levels of miR-206 expression have been correlated with tumor size and advanced pathological stage which suggested its use as a promising prognostic marker in breast cancer [22,23].…”

Section: Discussionmentioning

confidence: 90%

VEGF and KRAS are Potential Targets of miR-206 Modulation in Triple Negative Breast Cancer

Feky¹,

Ibrahim²,

Nassar³

et al. 2019

JCRT

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“…The protective effects of miR-206 on inhibition of cell proliferation and promotion of cell apoptosis have also been widely studied in various human diseases including knee articular osteoarthritis, prostate cancer, cervical cancer, triple negative breast cancer and etc. [37][38][39][40]. All these findings suggest the essential roles of miR-206 in the modulation of pathophysiology of human diseases including AMI.…”

Section: Discussionmentioning

confidence: 75%

The protective role of MiR-206 in regulating cardiomyocytes apoptosis induced by ischemic injury by targeting PTP1B

et al. 2020

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MicroRNAs play essential roles in the regulation and pathophysiology of acute myocardial infarction (AMI). The purpose of the present study was to assess the expression signature of miR-206 in rat heart with AMI and the corresponding molecular mechanism. The expression of miR-206 significantly decreased in the infarcted myocardial areas and in hypoxia-induced cardiomyocytes, compared with that in the noninfarcted areas. Overexpression of miR-206 decreased cardiomyocytes apoptosis and the down-regulation of miR-206 increased cardiomyocytes apoptosis in vitro. In addition, overexpression of miR-206 in rat heart in vivo remarkably reduced myocardial infarct size and cardiomyocytes apoptosis. We identified that miR-206 had a protective effect on cardiomyocytes apoptosis with the association of its target protein tyrosine phosphatase 1B (PTP1B). Gain-of-function of miR-206 inhibited PTP1B expression and loss-of-function of miR-206 up-regulated PTP1B expression. Furthermore, overexpression of PTP1B significantly increased cardiomyocytes apoptosis. These results together suggest the protective effect of miR-206 against cardiomyocytes apoptosis induced by AMI by targeting PTP1B.

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“…The specific molecular mechanism is related to the direct regulation of proto-oncogene/tumor suppressor gene and ncRNA expression by HDAC9. The currently known tumor suppressor gene P53 [44], deacetylated forkhead box gene O1 (FoxO1) [48], sex determining region Y-box 9 protein (SOX9) [49] and transcriptional coactivator with PDZ-binding motif (TAZ) [50] are potential target genes of HDAC9; changes in HDAC9 expression affect the transcription of target genes, thereby activating downstream signaling pathways, such as those involving the oncogenes Ras, VEGF, MAPK and EGFR, to promote tumor cell proliferation [51]. HDAC9 has been rarely studied in the context of HCC; most publications have focused on its relationship with miRNA.…”

Section: Rbm8a (Y 14)mentioning

confidence: 99%

Mechanism and molecular network of RBM8A-mediated regulation of oxaliplatin resistance in hepatocellular carcinoma via EMT

Lin

Liang

Zhang

et al. 2020

Preprint

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Epithelial-mesenchymal transition (EMT) has been shown to be closely associated with Oxaliplatin (OXA) resistance. Previous study found that RBM8A is highly expressed in HCC and induce EMT, suggesting that it may be involved in the regulation of OXA resistance in HCC. However, the accurate mechanism has not been concluded. In our study, ectopic expression and silencing of RBM8A were performed to explore its function. The OXA resistance potential of RBM8A and its downstream pathway was investigated using in vitro and in vivo models. The results showed that RBM8A overexpression induced EMT in OXA-resistant HCC cells, thereby affecting cell proliferation, apoptosis, migration, and invasion and promoting OXA resistance in vivo and in vitro. Moreover, whole-genome microarrays combined with bioinformatics analysis revealed that RBM8A has a wide range of transcriptional regulatory capabilities in drug-resistant HCC, including the ability to regulate several important tumor-related signaling pathways. Histone deacetylase 9 (HDAC9) is an important mediator of RBM8A activity related to OXA resistance. These data suggest that RBM8A and its related regulatory pathway represent potential markers of OXA resistance and therapeutic targets in HCC. BackgroundHepatocellular carcinoma (HCC) is a highly lethal cancer; although it has the sixth highest incidence of malignant tumors globally, its mortality rate ranks second among all cancers [1]. The advent of the molecularly targeted drug sorafenib has opened the door to advanced HCC drug therapies, but the objective response rate (ORR) and progression-free survival (PFS) for first-line therapies are limited and expensive to administer[2]. HCC is extremely complicated and refractory, and the difficulty in successfully treating it also highlights the necessity and importance of multiple methods and multidisciplinary comprehensive treatments, including systemic chemotherapy.The EACH trial and subsequent basic experiments and clinical trials have confirmed that OXA-based systemic chemotherapy for Asian patients with advanced HCC can improve the objective efficiency and has good tolerance and safety, a high cost-effectiveness ratio and easy clinical promotion; therefore, OXA is recognized as the most effective chemotherapy for HCC [3,4]. Even so, the effectiveness of OXA against HCC is still less than 20%, which is unsatisfactory. OXA resistance has 4 become a tremendous obstacle in the treatment of HCC. Identifying key targets affecting oxaliplatin resistance and its related signaling pathways and understanding their mechanism of action have become key issues to be solved urgently.Epithelial-mesenchymal transition (EMT) refers to the biological process by which epithelial cells gradually lose cell-cell adhesions and undergo a specific transformation to obtain characteristics of a strong mesenchymal phenotype, such as movement and migration; this process is closely related to the occurrence and development of a variety of tumors [5]. Ma et al.[6] reported that OXA-resistant HCC cells sh...

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HDAC9 overexpression confers invasive and angiogenic potential to triple negative breast cancer cells via modulating microRNA-206

Cited by 37 publications

References 44 publications

VEGF and KRAS are Potential Targets of miR-206 Modulation in Triple Negative Breast Cancer

VEGF and KRAS are Potential Targets of miR-206 Modulation in Triple Negative Breast Cancer

The protective role of MiR-206 in regulating cardiomyocytes apoptosis induced by ischemic injury by targeting PTP1B

Mechanism and molecular network of RBM8A-mediated regulation of oxaliplatin resistance in hepatocellular carcinoma via EMT

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