HDAC2 and HDAC5 Up-Regulations Modulate Survivin and miR-125a-5p Expressions and Promote Hormone Therapy Resistance in Estrogen Receptor Positive Breast Cancer Cells

Huang, Wen-Cheng; Tsai, Yu‐Hsuan; Chen, Shang Hung; Kuo, Ching Wen; Kuo, Yiyo; Lee, Kuo Ting; Chen, Wen Chung; Wu, Pei; Chuang, Chun Yu; Cheng, Sheng-Shung; Lin, Chun Hui; Leung, Euphemia; Chang, Yung Sheng; Cheung, Chun Hei Antonio

doi:10.3389/fphar.2017.00902

Cited by 31 publications

(48 citation statements)

References 57 publications

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“…It has been demonstrated that the epigenetic modulators could modulate the miR‐125‐5p expression,13, 25, 26 and its promoter is hypermethylated in glioma cells 27. We analysed the miR‐125a‐5p methylation status in gastric cancer tissues and adjacent non‐tumour tissues.…”

Section: Resultsmentioning

confidence: 99%

“…These data showed that overexpressing Furthermore, miR-125a-5p has been validated to prevent the cancer cell progression. [10][11][12][13][14][15][16][17][18][19]23,24 However, the underlying mechanism of the low expression of miR-125a-5p in gastric cancer remains unknown.…”

Section: Overexpressing Mir-125a-5p Suppresses Gastric Cancer Develmentioning

confidence: 99%

“…and miR-125a-5p uncovered in the current study, it has also been demonstrated HDACs and Sirtuins are also involved into this process. 13,25,26 Overexpessing miR-125a-5p could self-activate the silenced miR-125a-5p in gastric cancer cells, resulting in cancer suppression in vitro and in vivo. The data here showed that the miR-125a-5p might be not only the potential prognostic value as a tumour biomarker but also potential therapeutic targets in gastric cancer.…”

Section: Overexpressing Mir-125a-5p Suppresses Gastric Cancer Develmentioning

confidence: 99%

“…23,24 However, the underlying mechanism of the low expression of miR-125a-5p in gastric cancer remains unknown. It has been demonstrated that some epigenetic modulators could modulate the miR-125-5p expression, such as HDACs (histone deacetylases), 13,25 or be modulated by miR-125-5p, such as Sirtuins. 26 Furthermore, the putative promoter regions the miR-125a-5p are embedded in CpG islands and are hypermethylated in glioma cells.…”

mentioning

confidence: 99%

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Retracted: Epigenetic silenced miR‐125a‐5p could be self‐activated through targeting Suv39H1 in gastric cancer

Cai

Chen

Shen

et al. 2018

J Cellular Molecular Medi

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Emerging evidence suggests that microRNAs (miRNAs) serve an important role in tumorigenesis and development. Although the low expression of miR‐125a‐5p in gastric cancer has been reported, the underlying mechanism remains unknown. In the current study, the low expression of miR‐125a‐5p in gastric cancer was verified in paired cancer tissues and adjacent non‐tumour tissues. Furthermore, the GC islands in the miR‐125a‐5p region were hypermethylated in the tumour tissues. And the hypermethylation was negatively correlated with the miR‐125a‐5p expression. Target gene screening showed that the histone methyltransferase Suv39H1 was one of the potential target genes. In vitro studies showed that miR‐125a‐5p could directly suppress the Suv39H1 expression and decrease the H3K9me3 levels. On the other hand, the Suv39H1 could induce demethylation of miR‐125a‐5p, resulting in re‐activation of miR‐125a‐5p. What is more, overexpessing miR‐125a‐5p could also self‐activate the silenced miR‐125a‐5p in gastric cancer cells, which suppressed cell migration, invasion and proliferation in vitro and inhibited cancer progression in vivo. Thus, we uncovered here that the epigenetic silenced miR‐125a‐5p could be self‐activated through targeting Suv39H1 in gastric cancer, suggesting that miR‐125a‐5p might be not only the potential prognostic value as a tumour biomarker but also potential therapeutic targets in gastric cancer.

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Section: Resultsmentioning

confidence: 99%

Section: Overexpressing Mir-125a-5p Suppresses Gastric Cancer Develmentioning

confidence: 99%

Section: Overexpressing Mir-125a-5p Suppresses Gastric Cancer Develmentioning

confidence: 99%

mentioning

confidence: 99%

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Retracted: Epigenetic silenced miR‐125a‐5p could be self‐activated through targeting Suv39H1 in gastric cancer

Cai

Chen

Shen

et al. 2018

J Cellular Molecular Medi

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“…It is highly expressed in embryonic tissues (e.g. neuronal precursor cells and embryonic fibroblasts) and tumors (including both cancer cells and cancer stem cells), and its expression is associated with tumor cell differentiation, proliferation, invasion, and metastasis [3][4][5][6][7][8][9][10][11]. Interestingly, a few studies revealed that BIRC5 also plays an important role in neural cell proliferation after traumatic brain injury and in cardiomyocytes survival maintenance after cardiac injury [12][13][14][15].…”

Section: Introductionmentioning

confidence: 99%

BIRC5/Survivin is a novel ATG12–ATG5 conjugate interactor and an autophagy-induced DNA damage suppressor in human cancer and mouse embryonic fibroblast cells

et al. 2019

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2020) BIRC5/Survivin is a novel ATG12-ATG5 conjugate interactor and an autophagy-induced DNA damage suppressor in human cancer and mouse embryonic fibroblast cells, Autophagy, 16:7, 1296-1313, ABSTRACT BIRC5/Survivin is known as a dual cellular functions protein that directly regulates both apoptosis and mitosis in embryonic cells during embryogenesis and in cancer cells during tumorigenesis and tumor metastasis. However, BIRC5 has seldom been demonstrated as a direct macroautophagy/autophagy regulator in cells. ATG7 expression and ATG12-ATG5-ATG16L1 complex formation are crucial for the phagophore elongation during autophagy in mammalian cells. In this study, we observed that the protein expression levels of BIRC5 and ATG7 were inversely correlated, whereas the expression levels of BIRC5 and SQSTM1/p62 were positively correlated in normal breast tissues and tumor tissues. Mechanistically, we found that BIRC5 negatively modulates the protein stability of ATG7 and physically binds to the ATG12-ATG5 conjugate, preventing the formation of the ATG12-ATG5-ATG16L1 protein complex in human cancer (MDA-MB-231, MCF7, and A549) and mouse embryonic fibroblast (MEF) cells. We also observed a concurrent physical dissociation between BIRC5 and ATG12-ATG5 (but not CASP3/caspase-3) and upregulation of autophagy in MDA-MB-231 and A549 cells under serum-deprived conditions. Importantly, despite the fact that upregulation of autophagy is widely thought to promote DNA repair in cells under genotoxic stress, we found that BIRC5 maintains DNA integrity through autophagy negative-modulations in both human cancer and MEF cells under non-stressed conditions. In conclusion, our study reveals a novel role of BIRC5 in cancer cells as a direct regulator of autophagy. BIRC5 may act as a "bridging molecule", which regulates the interplay between mitosis, apoptosis, and autophagy in embryonic and cancer cells.

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Histone deacetylase HDAC2 regulates microRNA‐125a expression in neuroblastoma

et al. 2022

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Background: Neuroblastoma (NB) is an infrequent childhood malignancy of the peripheral sympathetic nervous system and is accountable for about 10% of pediatric tumors. microRNA (miR)-125a has been implicated to serve as a tumor suppressor in various cancers. Herein, we set out to ascertain whether miR-125a exerts antitumor effects in NB.Methods: Downregulated miRNAs were identified by miRNA microarray analysis of NB tissues and paracancerous tissues. The expression of miR-125a in NB tissues and cells was detected by reverse transcription-quantitative (RT-q) PCR, followed by prognostic analysis. Gene Ontology (GO) enrichment analysis was performed on target genes of differentially expressed miRNAs. Cell proliferation, apoptosis, and differentiation were detected by cell counting kit-8 (CCK-8), Hoechst staining, immunofluorescence, and western blot. NB cells were injected into nude mice to detect tumorigenic, apoptotic, and differentiation activities in vivo. Dual-luciferase assay and chromatin immunoprecipitation (ChIP) were carried out to verify the binding relationship between miR-125a and PHOX2B or histone deacetylases 2 (HDAC2), respectively. Finally, rescue experiments were conducted. Results: miR-125a was downregulated in NB tissues and cells, which was associated with poor prognosis. miR-125a reduced NB cell proliferation and augmented apoptosis and differentiation. NB cells with miR-125a overexpression decreased cell tumorigenesis and increased apoptosis and differentiation in xenograft tumor tissues. miR-125a targeted PHOX2B, which was highly expressed in NB tissues and cells. HDAC2, highly expressed in NB tissues and cells, repressed miR-125a transcription through histone deacetylation. Overexpression of HDAC2 or PHOX2B rescued the effects of miR-125a on NB cell proliferation, apoptosis, and differentiation. Conclusion: HDAC2 inhibited miR-125a transcription through deacetylation, and miR-125a suppressed NB development through binding to PHOX2B.

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HDAC2 and HDAC5 Up-Regulations Modulate Survivin and miR-125a-5p Expressions and Promote Hormone Therapy Resistance in Estrogen Receptor Positive Breast Cancer Cells

Cited by 31 publications

References 57 publications

Retracted: Epigenetic silenced miR‐125a‐5p could be self‐activated through targeting Suv39H1 in gastric cancer

Retracted: Epigenetic silenced miR‐125a‐5p could be self‐activated through targeting Suv39H1 in gastric cancer

BIRC5/Survivin is a novel ATG12–ATG5 conjugate interactor and an autophagy-induced DNA damage suppressor in human cancer and mouse embryonic fibroblast cells

Histone deacetylase HDAC2 regulates microRNA‐125a expression in neuroblastoma

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