Oncogenic Potential of the Dual-Function Protein MEX3A

Lederer, Marcell; Müller, Simon; Glaß, Markus; Bley, Nadine; Ihling, Christian; Sinz, Andrea; Hüttelmaier, Stefan

doi:10.3390/biology10050415

Cited by 15 publications

(13 citation statements)

References 91 publications

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“…MEX3A has been reported to facilitate mRNA decay or protein degradation of tumor suppressors involved in cell cycle, cell survival and apoptosis via its RNA-binding capacity or E3 ligase activity, respectively ( 44 ). We found that depletion of MEX3A did not affect p53 mRNA level ( Fig.…”

Section: Resultsmentioning

confidence: 99%

MEX3A Mediates p53 Degradation to Suppress Ferroptosis and Facilitate Ovarian Cancer Tumorigenesis

et al. 2022

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Epithelial ovarian cancer (OC) is a highly heterogeneous and malignant female cancer with an overall low survival rate. Mutations in p53 are prevalent in the major OC histotype, high-grade serous ovarian carcinoma (HGSOC), while p53 mutations are much less frequent in other OC subtypes, particularly in ovarian clear cell carcinoma (OCCC). Advanced stage OCCC with wildtype (WT) p53 has a worse prognosis and increased drug resistance, metastasis, and recurrence than HGSOC. The mechanisms responsible for driving the aggressiveness of WT p53-expressing OC remain poorly understood. Here, we found that upregulation of MEX3A, a dual-function protein containing a RING finger domain and an RNA binding domain, was critical for tumorigenesis in WT p53-expressing OC. MEX3A overexpression enhanced the growth and clonogenicity of OCCC cell lines. In contrast, depletion of MEX3A in OCCC cells, as well as ovarian teratocarcinoma cells, reduced cell survival and proliferative ability. MEX3A depletion also inhibited tumor growth and prolonged survival in orthotopic xenograft models. MEX3A depletion did not alter p53 mRNA level but did increase p53 protein stability. MEX3A-mediated p53 protein degradation was crucial to suppress ferroptosis and enhance tumorigenesis. Consistently, p53 knockdown reversed the effects of MEX3A depletion. Together, our observations identified MEX3A as an important oncogenic factor promoting tumorigenesis in OC cells expressing WT p53.

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Section: Resultsmentioning

confidence: 99%

MEX3A Mediates p53 Degradation to Suppress Ferroptosis and Facilitate Ovarian Cancer Tumorigenesis

et al. 2022

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“…MEX3A, an RNA-binding protein, is overexpressed in multiple cancers like pancreatic, breast, and lung. 39 It was reported to promote cancer proliferation by stabilizing CDK6 or LAMA2 mRNA. 40 Bioinformatic analysis and experimental validation confirmed that MEX3A was overexpressed in HCC.…”

Section: Discussionmentioning

confidence: 99%

Establishment and Validation of a Four-stress Granule-related Gene Signature in Hepatocellular Carcinoma

Li¹,

Fan²,

Zhao³

et al. 2023

J Clin Transl Hepatol

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Background and Aims Stress granules (SGs) as membrane-less cytoplasmic foci formed in response to unfavorable external stimuli could promote cancer cells to adapt to hostile environments. Hepatocellular carcinoma (HCC) is prone to be highly aggressive once diagnosed, which markedly reduces patient survival time. Therefore, it is crucial to develop valid diagnostic markers to prognosticate HCC patient prognosis, which promotes individualized precision therapeutics in HCC. Considering the pro-tumorigenic activity of SGs, it is of great potential value to construct a prognostic tool for HCC based on the expression profiles of SG-related genes (SGGs). Methods Bioinformatic analysis was employed to establish an SGG-based prognostic signature. Western blotting and real-time polymerase chain reaction assays were used to assess the expression patterns of the related SGGs. Loss-of-function experiments were performed to analyze the effect of the SGGs on SG formation and cell survival. Results A four-SGG signature ( KPNA2 , MEX3A , WDR62 , and SFN ) targeting HCC was established and validated to exhibit a robust performance in predicting HCC prognosis. Consistently, all four genes were further found to be highly expressed in human HCC tissues. More important, we demonstrated that individually knocking down the four SGGs significantly reduced HCC cell proliferation and metastasis by compromising the SG formation process. Conclusions We developed an SGG-based predictive signature that can be used as an independent prognostic tool for HCC. The strong predictive power of this signature was further elucidated by the carcinogenic activity of KPNA2 , MEX3A , WDR62 , and SFN in HCC cells by regulating SG formation.

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“…HMGA2 protein is a transcriptional regulator that can affect radiotherapy sensitivity by promoting DNA repair ( 22 ). Muscle EXcess 3A ( MEX3A ) is an RNA-binding protein that mediates MAPK/ERK pathway activation, promoting tumor proliferation and anti-apoptosis, and affecting radiotherapy sensitivity ( 45 ). All of these mutated genes are associated with DNA repair and cellular regulation, thus affecting radiotherapy sensitivity and promoting the development of radiotherapy resistance.…”

Section: Hpv− Tumorsmentioning

confidence: 99%

HPV and radiosensitivity of cervical cancer: a narrative review

Huang¹,

Zou²,

Guo³

et al. 2022

Ann Transl Med

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Background and Objective: Cervical cancer (CC), the most common gynecological malignancy, is divided into two categories: human papillomavirus-related [HPV positive (HPV+)] and non-HPV-related [HPV negative (HPV−)]. Compared with HPV− CC, HPV+ CC has better radiosensitivity and prognosis. We conducted a literature search and summarized relevant studies to explore the detailed mechanisms by which HPV+ improves the prognosis of CC compared to HPV−. Methods: PubMed was used to search the literature on human papillomavirus, cervical cancer, and radiotherapy up to June 2022.

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Oncogenic Potential of the Dual-Function Protein MEX3A

Cited by 15 publications

References 91 publications

MEX3A Mediates p53 Degradation to Suppress Ferroptosis and Facilitate Ovarian Cancer Tumorigenesis

MEX3A Mediates p53 Degradation to Suppress Ferroptosis and Facilitate Ovarian Cancer Tumorigenesis

Establishment and Validation of a Four-stress Granule-related Gene Signature in Hepatocellular Carcinoma

HPV and radiosensitivity of cervical cancer: a narrative review

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