Heme oxygenase promotes B‐Raf‐dependent melanosphere formation

Jasmer, Kimberly J.; Hou, Jie; Mannino, Philip; Cheng, Jianlin; Hannink, Mark

doi:10.1111/pcmr.12905

Cited by 8 publications

(16 citation statements)

References 120 publications

(156 reference statements)

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“…HMOX2 is an isoenzyme of heme oxygenase, which catalyzes the degradation of heme into ferrous iron and other substances [ 43 ]. Activation of HMOX2 by oncogenic BRAF promotes the increase of melanospheres in melanoma [ 44 ]. HSPB1 (heat shock protein beta-1) can be mediated by Protein kinase C, which in turn plays a negative regulatory role in ferroptosis [ 45 ].…”

Section: Discussionmentioning

confidence: 99%

Comprehensive analysis of ferroptosis-related genes and prognosis of cutaneous melanoma

Liu

et al. 2022

BMC Med Genomics

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Background Cutaneous Melanoma (CM) is a malignant disease with increasing incidence and high mortality. Ferroptosis is a new kind of cell death and related to tumor blood and lymphatic metastasis. This study aims at using bioinformatics technology to construct a prognostic signature and identify ferroptosis-related biomarkers to improve the prognosis and treatment of cutaneous melanoma. Methods We used bioinformatics tools to analyze RNA sequencing expression data with clinical information from multiple databases, utilized varieties of statistical methods to construct a ferroptosis-related prognostic signature of cutaneous melanoma and screened out specific genes with independent prognostic ability. Results We obtained 22 ferroptosis-related (P < 0.05) prognostic DEGs in the uniCox regression analysis, among which 10 high-expressed genes (ATG5, CHAC1, FANCD2, FBXL5, HMOX2, HSPB1, NQO1, PEBP1, PRNP, SLC3A2) were screened out by LASSO regression analysis to establish a predictive model. Meanwhile, the ferroptosis-related signature and the nomogram we drew performed an excellent performance based on Kaplan–Meier (K–M), Receiver operating characteristic (ROC) and calibration curves. Univariate and multivariable cox analyses displayed that our model was greater than other prognostic features. GO and KEGG analyses revealed that 10-biomarker signature was mainly related to epidermis differentiation and immunity. ssGSEA analysis indicated that the immune status between the two risk groups was highly different. Besides, we found that two genes (CP, ZEB1) had independent prognostic ability and can be applied for drug research. Both genes were highly related to immunity. GSEA illustrated that ZEB1 may be involved in cellular functions such as proliferation, apoptosis, and migration, while CP was closely connected to immune cell related functions. Conclusion The present study suggested a 10-biomarker signature can be clinically used to predict the prognosis of cutaneous melanoma, which was better than conventional factors. CP and ZEB1 were independent prognostic genes and can be applied to guide treatment. In addition, ZEB1 mutation was highly related to overall survival in cutaneous melanoma, while CP may be associated with tumor progression. Our study comprehensively analyzed the relationship between iron metabolism, ferroptosis-related genes, and the prognosis of cutaneous melanoma, provided new insight for molecular mechanisms and treatment of ferroptosis and cutaneous melanoma.

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Section: Discussionmentioning

confidence: 99%

Comprehensive analysis of ferroptosis-related genes and prognosis of cutaneous melanoma

Liu

et al. 2022

BMC Med Genomics

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“…In breast cancer, increased expression of HO-1 augments the aggressiveness of CD24 low CD44 high CSC fraction and marks mammospheres [ 63 ]. Recent data on human melanoma proved that HO-1 activity promotes the formation of melanospheres [ 64 ]. Consistently, we observed that inhibition of HO-1 activity with SnPP abolished non-adherent growth ( Figure 1 a) without changing the HO-1 expression (data not shown), which highlights the important role of enzymatic activity of heme oxygenase in the formation of melanospheres by murine melanoma.…”

Section: Discussionmentioning

confidence: 99%

Heme Oxygenase-1 Has a Greater Effect on Melanoma Stem Cell Properties Than the Expression of Melanoma-Initiating Cell Markers

Kusienicka

Bukowska-Straková

Cieśla

et al. 2022

IJMS

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Melanoma-initiating cells (MICs) contribute to the tumorigenicity and heterogeneity of melanoma. MICs are identified by surface and functional markers and have been shown to display cancer stem cell (CSC) properties. However, the existence of MICs that follow the hierarchical CSC model has been questioned by studies showing that single unselected melanoma cells are highly tumorigenic in xenotransplantation assays. Herein, we characterize cells expressing MIC markers (CD20, CD24, CD133, Sca-1, ABCB1, ABCB5, ALDHhigh) in the B16-F10 murine melanoma cell line. We use flow cytometric phenotyping, single-cell sorting followed by in vitro clonogenic assays, and syngeneic in vivo serial transplantation assays to demonstrate that the expression of MIC markers does not select CSC-like cells in this cell line. Previously, our group showed that heme-degrading enzyme heme oxygenase-1 (HO-1) can be upregulated in melanoma and increase its aggressiveness. Here, we show that HO-1 activity is important for non-adherent growth of melanoma and HO-1 overexpression enhances the vasculogenic mimicry potential, which can be considered protumorigenic activity. However, HO-1 overexpression decreases clone formation in vitro and serial tumor initiation in vivo. Thus, HO-1 plays a dual role in melanoma, improving the progression of growing tumors but reducing the risk of melanoma initiation.

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“…As a result, these data showed the inverse correlation standing between HO-1 expression and mice survival [ 15 , 34 ]. Corroborating this data, targeting HO-1 showed significant potential to counteract metastatic melanoma, given the outstanding role of Nrf2 and HO-1 enzymatic activity in melanosphere formation [ 35 ]. More broadly, HO-1 has been reported as an outstanding player promoting cellular proliferation in prostate, pancreatic, and hepatoma cancer cells [ 36 , 37 ].…”

Section: Discussionmentioning

confidence: 99%

Heme Oxygenase-1 Overexpression Promotes Uveal Melanoma Progression and Is Associated with Poor Clinical Outcomes

et al. 2022

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Uveal melanoma (UM) is the most common primary intraocular tumor in adults. To date, the main strategies to counteract its progression consist of focal radiation on the tumor site and ocular enucleation. Furthermore, many UM patients develop liver metastasis within 10 years following diagnosis, eventually resulting in a poorer prognosis for those patients. Dissecting the molecular mechanism involved in UM progression may lead to identify novel prognostic markers with significative clinical applications. The aim of the present study was to evaluate the role of Heme Oxygenase 1 (HO-1) in regulating UM progression. UM cell lines (92.1) were treated with Hemin (CONC e time), a strong inducer of HO-1, and VP13/47, a selective inhibitor of its enzymatic activity. Interestingly, our results showed an enhanced 92.1 cellular proliferation and wound healing ability following an HO-1 increase, overall unveiling the role played by this protein in tumor progression. Similar results were obtained following treatment with two different CO releasing molecules (CORM-3 and CORM-A1). These results were further confirmed in a clinical setting using our UM cohort. Our results demonstrated an increased median HO-1 expression in metastasizing UM when compared to nonmetastasizing patients. Overall, our results showed that HO-1 derived CO plays a major role in UM progression and HO-1 protein expression may serve as a potential prognostic and therapeutical factor in UM patients.

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Heme oxygenase promotes B‐Raf‐dependent melanosphere formation

Abstract: Reactive oxygen species (ROS) function as signaling molecules under physiological conditions, but excessive production of

Cited by 8 publications

References 120 publications

Comprehensive analysis of ferroptosis-related genes and prognosis of cutaneous melanoma

Comprehensive analysis of ferroptosis-related genes and prognosis of cutaneous melanoma

Heme Oxygenase-1 Has a Greater Effect on Melanoma Stem Cell Properties Than the Expression of Melanoma-Initiating Cell Markers

Heme Oxygenase-1 Overexpression Promotes Uveal Melanoma Progression and Is Associated with Poor Clinical Outcomes

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