Heme Oxygenase-1 Controls an HDAC4-miR-206 Pathway of Oxidative Stress in Rhabdomyosarcoma

Cieśla, Maciej; Marona, Paulina; Kozakowska, Magdalena; Jez, Mateusz; Seczyńska, Marta; Łoboda, Agnieszka; Bukowska-Straková, Karolina; Szade, Agata; Walawender, Magdalena; Kusior, Magdalena; Stępniewski, Jacek; Szade, Krzysztof; Krist, Bart; Yagensky, Oleksandr; Urbanik, Aleksandra; Kazanowska, Bernarda; Dulak, Józef; Józkowicz, Alicja

doi:10.1158/0008-5472.can-15-1883

Cited by 49 publications

(45 citation statements)

References 50 publications

(80 reference statements)

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“…However, no differences between cells of both genotypes were observed (Fig A). Since our recent studies revealed that HO‐1 can influence expression of miRNA molecules , the level of ESC‐specific miRNAs was further analyzed in Hmox1 +/+ and Hmox1 –/– iPSCs. Again, no differences in the expression of various miRNAs of miR‐290–295 cluster were observed (Fig.…”

Section: Resultsmentioning

confidence: 99%

Heme oxygenase‐1 affects generation and spontaneous cardiac differentiation of induced pluripotent stem cells

et al. 2018

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Cellular stress can influence efficiency of iPSCs generation and their differentiation. However, the role of intracellular cytoprotective factors in these processes is still not well known. Therefore, we investigated the effect of HO-1 (Hmox1) or Nrf2 (Nfe2l2), two major cytoprotective genes. Hmox1 fibroblasts demonstrated decreased reprogramming efficiency in comparison to Hmox1 cells. Reversely, pharmacological enhancement of HO-1 resulted in higher number of iPSCs colonies. Importantly, elevated level of both p53 and p53-regulated miR-34a and 14-3-3σ was observed in HO-1-deficient fibroblasts whereas downregulation of p53 in these cells markedly increased their reprogramming efficiency. In human fibroblasts HO-1 silencing also induced p53 expression and affected reprogramming outcome. Hmox1 and Hmox1 iPSCs similarly differentiated in vitro to cells originating from three germ layers, however, lower number of contracting cells was observed during this process in HO-1-deficient cells indicating attenuated cardiac differentiation. Importantly, silencing of Hmox1 in murine ESC using CRISPR/Cas-9 editing also impaired their spontaneous cardiac differentiation. Decreased reprogramming efficiency was also observed in Nrf2-lacking fibroblasts. Reversely, sulforaphane, a Nrf2 activator, increased the number of iPSCs colonies. However, both Nfe2l2 and Nfe2l2 iPSCs showed similar pluripotency and differentiation capacity. These results indicate that regulation of HO-1 expression can further optimize generation and cardiac differentiation of iPSCs. © 2018 IUBMB Life, 70(2):129-142, 2018.

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Section: Resultsmentioning

confidence: 99%

Heme oxygenase‐1 affects generation and spontaneous cardiac differentiation of induced pluripotent stem cells

et al. 2018

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“…Compared to CUR, the structure of DMC lacks one methoxy group directly linked to the benzene ring, as shown in Figure 1A. To investigate the pharmacological potential of DMC against OSCC, we examined short-term (24 h) and long-term treatment (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19) days) effects of DMC on the cell growth of primary SCC-9 and metastatic HSC-3 OSCC cells, respectively using thiazolyl blue tetrazolium bromide (MTT) and colony formation assays. As shown in Figure 1B, after 24 h, DMC treatment concentration dependently inhibited the cell proliferation of both OSCC cells, and the 50% growth inhibitory concentration (IC50) was around 50 µM.…”

Section: Dmc Exerts Antiproliferative Activity and Causes G2/m Cell Cmentioning

confidence: 99%

“…HO-1 was reported to be overexpressed or downregulated in different cancer types and has a multifaceted role in cancer development through regulating apoptosis, angiogenesis, and metastasis [11]. For example, the overexpression of HO-1 can enhance the proliferative or metastatic abilities of pancreatic cancer [12], melanomas [13], and rhabdomyosarcomas [14] in vitro and in vivo. In contrast, the overexpression of HO-1 exerts antiproliferative or anti-invasive abilities in breast, lung, and liver cancers [15][16][17].…”

Section: Introductionmentioning

confidence: 99%

Dual Targeting of the p38 MAPK-HO-1 Axis and cIAP1/XIAP by Demethoxycurcumin Triggers Caspase-Mediated Apoptotic Cell Death in Oral Squamous Cell Carcinoma Cells

Chien

Yang

et al. 2020

Cancers

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Demethoxycurcumin (DMC) is an curcumin analogue with better stability and higher aqueous solubility than curcumin after oral ingestion and has the potential to treat diverse cancers, including oral squamous cell carcinoma (OSCC). The aim of this study was to investigate the anticancer effects and underlying mechanisms of DMC against OSCC. We found that DMC suppressed cell proliferation via simultaneously inducing G2/M-phase arrest and cell apoptosis. Mechanistic investigations found that the downregulation of cellular IAP 1 (cIAP1)/X-chromosome-linked IAP (XIAP) and upregulation of heme oxygenase-1 (HO-1) were critical for DMC-induced caspase-8/-9/-3 activation and apoptotic cell death. Moreover, p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK)1/2 were activated by DMC treatment in OSCC cells, and only the inhibition of p38 MAPK significantly abolished DMC-induced HO-1 expression and caspase-8/-9/-3 activation. The analyses of clinical datasets revealed that patients with head and neck cancers expressing high HO-1 and low cIAP1 had the most favorable prognoses. Furthermore, an combinatorial treatment of DMC with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, gefitinib, significantly enhanced the inhibitory effect of gefitinib on the proliferation of OSCC cells. Overall, the current study supported an role for DCM as part of an therapeutic approach for OSCC through suppressing IAPs and activating the p38-HO-1 axis.

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“…For example, miR-206 was downregulated in breast cancer, and suppressed cell proliferation by targeting cyclinD2 (13). Moreover, miR-206 also mediated cardiac hypotrophy (14) and oxidative stress (15). Study has proved that miR-206 mediated in the osteogenic differentiation in steroid-induced avascular necrosis of femoral head.…”

Section: Introductionmentioning

confidence: 98%

Downregulated SOX9 mediated by miR‑206 promoted cell apoptosis in Legg-Calvï¿½-Perthes disease

Luo

Han

et al. 2017

Oncol Lett

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Abstract. Legg-Calvé-Perthes disease (LCPD) commonly onsets in adolescents, and threatens their health. However, the potential mechanism underlying LCPD remains unclear. MicroRNA (miR)-206 and SRY-box 9 (SOX9) serve an important role in chondrocytes; however, their role in LCPD remains ambiguous. In the present study, whether miR-206 and SOX9 mediated cell apoptosis in dexamethasone (DEX)-induced LCPD was investigated. The chondrocytes of the LCPD and normal control group were isolated from clinical tissues. Reverse transcription-quantitative polymerase chain reaction was used to evaluate the expression of miR-206 and SOX9 mRNA. Western blotting was used to measure the protein level of SOX9. A combination of Annexin V-fluorescein isothiocyanate flow cytometry was used to assess cell apoptosis. The association between miR-206 and SOX9 was detected using a luciferase reporter assay. miR-206 was overexpressed while SOX9 was downregulated in chondrocytes treated with DEX obtained from patients with LCPD. miR-206 targeted SOX9 to regulate its expression. Overexpression of miR-206 promoted cell apoptosis in TC28, while it was reversed by SOX9 overexpression. TC28 cells pretreated with DEX significantly promoted cell apoptosis, while cells transfected with miR-206 inhibitor significantly reversed the effect; however, downregulated SOX9 abolished the effects of miR-206 inhibitor. SOX9 mediated by miR-206 possibly contributed to the pathogenesis of LCPD. The results of the present study suggest that miR-206 and SOX9 function as important therapeutic targets for the future of clinical therapy.

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Heme Oxygenase-1 Controls an HDAC4-miR-206 Pathway of Oxidative Stress in Rhabdomyosarcoma

Cited by 49 publications

References 50 publications

Heme oxygenase‐1 affects generation and spontaneous cardiac differentiation of induced pluripotent stem cells

Heme oxygenase‐1 affects generation and spontaneous cardiac differentiation of induced pluripotent stem cells

Dual Targeting of the p38 MAPK-HO-1 Axis and cIAP1/XIAP by Demethoxycurcumin Triggers Caspase-Mediated Apoptotic Cell Death in Oral Squamous Cell Carcinoma Cells

Downregulated SOX9 mediated by miR‑206 promoted cell apoptosis in Legg-Calvï¿½-Perthes disease

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