scholarly journals Nuclear Localization of BRAFV600E Is Associated with HMOX-1 Upregulation and Aggressive Behavior of Melanoma Cells

Cancers ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 311
Author(s):  
Mourad Zerfaoui ◽  
Eman Toraih ◽  
Emmanuelle Ruiz ◽  
Youssef Errami ◽  
Abdallah S. Attia ◽  
...  

Background: Previously, we have demonstrated that nuclear BRAFV600E is associated with melanoma aggressiveness and vemurafenib resistance. However, the underlying mechanisms of how nuclear localization of BRAFV600E promotes cell aggressiveness have not yet been investigated. Despite therapeutic advancements targeting cutaneous melanoma, unknown cellular processes prevent effective treatment for this malignancy, prompting an urgent need to identify new biological targets. This study aims to explore the association of inducible heme oxygenase 1 (HMOX-1) with nuclear BRAFV600E in promoting melanoma aggressiveness. Methods: Proteomics analysis was performed to identify the interacting partner(s) of nuclear BRAFV600E. Immunohistochemistry was applied to evaluate the levels of HMOX-1 and nuclear BRAFV600E expression in melanoma and adjacent healthy tissues. Immunofluorescence assessed the nuclear localization of BRAFV600E in vemurafenib-resistant A375R melanoma cells. Further study of HMOX-1 knockdown or BRAFV600E overexpression in melanoma cells suggested a role for HMOX-1 in the regulation of cell proliferation in vivo and in vitro. Finally, Western blot analysis was performed to confirm the pathway by which HMOX-1 mediates Akt signaling. Results: Proteomics results showed that HMOX-1 protein expression was 10-fold higher in resistant A375R cells compared to parental counterpart cells. In vitro and in vivo results illustrate that nuclear BRAFV600E promotes HMOX-1 overexpression, whereas HMOX-1 reduction represses melanoma cell proliferation and tumor growth. Mechanistic studies revealed that HMOX-1 was associated with nuclear BRAFV600E localization, thus promoting melanoma proliferation via a persistent activation of the AKT pathway. Conclusions: Our results highlight a previously unknown mechanism in which the nuclear BRAFV600E/HMOX-1/AKT axis plays an essential role in melanoma cell proliferation. Targeting HMOX-1 could be a novel method for treating melanoma patients who develop BRAF inhibitor resistance.

2010 ◽  
Vol 19 (11) ◽  
pp. 958-964 ◽  
Author(s):  
Zhiqi Song ◽  
Chun-Di He ◽  
Changkai Sun ◽  
Yanni Xu ◽  
Xin Jin ◽  
...  

BMC Cancer ◽  
2011 ◽  
Vol 11 (1) ◽  
Author(s):  
Mélissa Labelle-Côté ◽  
Julie Dusseault ◽  
Salma Ismaïl ◽  
Aude Picard-Cloutier ◽  
Peter M Siegel ◽  
...  

Author(s):  
Loreto B. Feril ◽  
Kazuki Yamaguchi ◽  
Yurika Ikeda-Dantsuji ◽  
Yukihiro Furusawa ◽  
Yoshiaki Tabuchi ◽  
...  

Oncogenesis ◽  
2018 ◽  
Vol 7 (11) ◽  
Author(s):  
Seung-Shick Shin ◽  
Byeong-Seon Jeong ◽  
Brian A. Wall ◽  
Jiadong Li ◽  
Naing Lin Shan ◽  
...  

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yingnan Liu ◽  
Yongqing Zhuang ◽  
Xiaokuan Fu ◽  
Chaofei Li

Abstract Background LncRNA POU3F3 (POU3F3) is overexpressed and plays oncogenic roles in esophageal squamous-cell carcinomas. LncRNA MEG3 (MEG3) has been characterized as a tumor suppressive lncRNA in different types of cancer. Our preliminary deep sequencing analysis revealed the inverse correlation between POU3F3 and MEG2 across melanoma tissues, indicating the interaction between them in melanoma. Therefore, this study was performed to investigate the crosstalk between POU3F3 and MEG3 in melanoma. Methods Tumor and adjacent healthy tissues collected from 60 melanoma patients were subjected to RNA extractions and RT-qPCRs to analyze the differential expression of POU3F3 and MEG2 in melanoma. In melanoma cells, POU3F3 and MEG2 were overexpressed to study the interactions between them. CCK-8 assays were performed to analyze the roles of POU3F3 and MEG2 in regulating melanoma cell proliferation. Results We found that POU3F3 was upregulated, while lncRNA MEG3 was downregulated in melanoma. Expression levels of POU3F3 and MEG3 were inversely correlated across tumor tissues. In vitro experiments showed that POU3F3 overexpression decreased MEG3 expression in melanoma cells, while MEG3 overexpression failed to affect POU3F3. POU3F3 overexpression increased melanoma cell proliferation, while MEG3 overexpression decreased melanoma cell proliferation. In addition, rescue experiments showed that MEG3 overexpression attenuated the enhancing effects of POU3F3 overexpression. Conclusion POU3F3 may promote melanoma cell proliferation by downregulating MEG3.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sahel N. Abduljauwad ◽  
Habib-ur-Rehman Ahmed ◽  
Vincent T. Moy

AbstractThe incidence of malignant melanoma has rapidly increased in the last two decades. There are many challenges associated with the current conventional therapies, including tumour size and location, the specificity of treatments, tumour resistance, non-mutually exclusive mutations, drug resistance, and many adverse side effects. Due to conventional therapies having several limitations, we have explored an alternative therapy such as nano-clays; nano-sized natural materials originating from clay fraction of the soil. Recently, clay nanoparticles have increasingly been used as a drug carrier for cancer treatment due to their high absorption, ability to engulf microbes, and low toxicity. In this study, we evaluated the effects of a nano-clays mix on melanoma cell proliferation and cell viability in vitro and melanoma growth in vivo xenograft animal model. The in vitro study revealed that nano-clay treatments significantly reduced melanoma cell proliferation and cell viability in a dosage-dependent manner. The in vivo tumour xenograft model demonstrated that nano-clay mix treatment led to significantly reduced tumour size and weight, decreased tumour cell mitosis, and induced tumour necrosis. These processes owe to the most probable changes in the membrane potential of the cancer cells once nano-clays bind with the former through the high non-specific adhesion characteristic of the cancer cells. As the data suggest an important role of nano-clays as an inhibitor of melanoma cell proliferation and survival, these prove to be a natural and effective medicine for the treatment of melanoma. The proven compatibility of nano-clays with the human cells with little side-effects makes them a highly preferred choice for the treatment of melanoma and probably other types of cancers.


2011 ◽  
Vol 30 (5) ◽  
pp. 1849-1864 ◽  
Author(s):  
Kristopher R. Koch ◽  
Chen-Ou Zhang ◽  
Piotr Kaczmarek ◽  
Joseph Barchi ◽  
Li Guo ◽  
...  

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