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Malignant melanoma (MM) causes 80% of skin cancer-related deaths and becomes the most lethal type of skin cancer. The molecular mechanism of MM is still not clear. This study aimed to reveal the relationship between MM and EIF3H. Clinical specimens were collected to preliminarily explore the role of EIF3H in MM. MM cell lines with EIF3H knockdown were constructed for investigating the effects of EIF3H on cell proliferation, apoptosis, cell cycle and cell motility. Mice xenograft model was constructed for verification in vivo. We found that EIF3H was obviously upregulated in MM tissues compared with normal skin tissues, which was correlated with tumor stage and risk of lymphatic metastasis. The in vitro results indicated that silencing EIF3H in MM cells could significantly suppress cell proliferation, promote cell apoptosis and induce cell cycle arrest. Moreover, EIF3H knockdown significantly restrained cell motility through regulating EMT-related proteins. The effects of EIF3H knockdown were also verified in mice xenograft model, which were represented by slower growth rate, smaller volume and lighter weight of tumors. Therefore, EIF3H was identified as a critical factor in the development and progression of MM which may be used as a novel therapeutic target in the treatment of MM., (Copyright © 2021. Published by Elsevier Inc.)

Hepatocellular carcinoma (HCC) is one of the most prevalent and lethal human malignancies, and with quite limited treatment alternatives. The proteasome is responsible for most of the protein degradation in eukaryotic cells and required for the maintenance of intracellular homeostasis. However, its potential role in HCC is largely unknown. In the current study, we identified eukaryotic translation initiation factor 3 subunit H (EIF3H), belonging to the JAB1/MPN/MOV34 (JAMM) superfamily, as a bona fide deubiquitylase of O-GlcNAc transferase (OGT) in HCC. We explored that EIF3H was positively associated with OGT in HCC and was related to the unfavorable prognosis. EIF3H could interact with, deubiquitylate, and stabilize OGT in a deubiquitylase-dependent manner. Specifically, EIF3H was associated with the GT domain of ERα via its JAB/MP domain, thus inhibiting the K48-linked ubiquitin chain on OGT. Besides, we demonstrated that the knockdown of EIF3H significantly reduced OGT protein expression, cell proliferation and invasion, and caused G1/S arrest of HCC. We also found that the deletion of EIF3H prompted ferroptosis in HCC cells. Finally, the effects of EIF3H depletion could be reversed by further OGT overexpression, implying that the OGT status is indispensable for EIF3H function in HCC carcinogenesis. In summary, our study described the oncogenic function of EIF3H and revealed an interesting post-translational mechanism between EIF3H, OGT, and ferroptosis in HCC. Targeting the EIF3H may be a promising approach in HCC. 6aJiHquPswT5dhvMxQLovC Video Abstract [ABSTRACT FROM AUTHOR]

Eukaryotic translation initiation factor 3 subunit H ( EIF3H) is required for the progression of several types of cancer. However, little is known about the function of EIF3H in gastric carcinoma. To address this issue, in the present study, we investigated EIF3H genetic alterations in and expression of EIF3H in gastric cancer tissue samples using cBioPortal and Oncomine databases. Endogenous EIF3H expression was knocked down in MGC80-3 and AGS gastric cancer cell lines by lentivirus-mediated RNA interference. We confirmed the knockdown efficiency by quantitative real-time PCR and western blotting and evaluated the effects of EIF3H silencing on cell proliferation of gastric cancer with the cell viability and colony formation assays and by flow cytometry. The OncoPrint of EIF3H generated using cBioPortal indicated that EIF3H genetic alterations (mutation, deletion and amplification) were present in two gastric cancer sample sets. The Oncomine analysis revealed that EIF3H mRNA level was upregulated in gastric cancer tissues. EIF3H knockdown inhibited cell proliferation and colony formation in gastric cancer lines and led to cell cycle arrest at the G0/G1 phase, while inducing apoptosis via up- and downregulation of pro- and anti-apoptotic factors, respectively. These results indicate that EIF3H can serve as a novel therapeutic target for the clinical treatment of gastric cancer. [ABSTRACT FROM AUTHOR]