RAB5C, a new mRNA binding target of HuR, regulates breast cancer cell proliferation

Wang, Zhenzhen; Li, Fang; Zhang, Huahua; Hu, Xiaoyi; Chen, Yanke; Huang, Chen

doi:10.1002/cbin.11969

Cited by 4 publications

(3 citation statements)

References 19 publications

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“…RAC1 and CDC42 acted together as downstream signals of RAS gene in the MAPK pathway to regulate cytoskeletal movement [33]. This may be a possible reason for the enhanced proliferation of HER2 L796P [34]. In phosphorylated proteomics studies, we found more differentially expressed protein sites related to MAPK and PI3K/AKT/TOR pathways.…”

Section: Discussionmentioning

confidence: 97%

Rare HER2 L796P missense mutation promotes the growth and oncogenic signaling in breast cancer cells

Zhang,

Shi,

Zheng

et al. 2023

Proteomics Clinical Apps

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PurposeThis research aimed to find potential HER2 mutations that would have an impact on breast cancer and investigate the underlying mechanism.Experimental designThis study first investigated 238 pairs of breast cancer and para‐cancerous tissue samples from patients on the targeted next‐generation sequencing (tNGS) platform. CCK‐8 and clone formation assay were used to investigate whether the mutation exerts proliferative effects on breast cancer cells. In addition, mass spectrometry‐based comparative proteomic and phosphoproteomic analyses of the mutation types and wild types of MCF‐7 cell lines were carried out.ResultsAmong the identified mutations, a new mutation HER2 L796P promoted the proliferation of breast cancer cells and had resistance to lapatinib using CCK‐8 cell proliferation assay and clone formation assay. The bioinformatic analysis showed that RAS family proteins and ERK phosphorylated proteins significantly increased in the L796P mutant cells. The Gene Ontology (GO) analysis revealed that L796P mutation affected the function of breast cancer at the level of upstream genes in the MAPK and PI3K‐AKT‐TOR pathways.Conclusions and clinical relevanceThis study demonstrated that a rare mutation HER2 L796P could be a potential therapeutic target for the clinical management of breast cancer.

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Section: Discussionmentioning

confidence: 97%

Rare HER2 L796P missense mutation promotes the growth and oncogenic signaling in breast cancer cells

Zhang,

Shi,

Zheng

et al. 2023

Proteomics Clinical Apps

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“…It primarily involves vesicle docking and fusion processes, ensuring vesicles bind to their correct receptors. Wang et al discovered that RAB5C is a new mRNA binding target of HuR, regulating breast cancer cell proliferation [40] . Zhang et al found that RAB5C is a tumor suppressor in thyroid cancer [41] .…”

Section: Discussionmentioning

confidence: 99%

Identification of a novel mitophagy-related signature for predicting clinical prognosis and immunotherapy of osteosarcoma

Xu,

Zhao,

Zhao

et al. 2024

Preprint

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Background Osteosarcoma (OS) is a highly aggressive malignancy characterized by a poor prognosis. Mitochondrial autophagy (mitophagy) has been implicated in tumor initiation, progression, and response to therapy, highlighting it a potential prognostic indicator and therapeutic target in cancers. Despite this, the precise mechanisms underlying mitophagy in osteosarcoma remain enigmatic. This research aims to develop a mitophagy-associated signature to guide therapeutic strategies and prognosis estimations. Methods Clinical and transcriptome data for patients with osteosarcoma and skeletal muscle tissue were retrieved from UCSC Xena and GTEx. Mitophagy-related genes (MRGs) were obtained from the Kyoto Encyclopedia of Genes and Genomes (KEGG) website. A predictive risk model was constructed using the Least Absolute Shrinkage and Selection Operator (LASSO) algorithm and Cox regression analysis. To delve into the fundamental gene expression mechanisms, we employed Gene Ontology (GO), KEGG, and Gene Set Enrichment Analysis (GSEA). Moreover, the different immune-related activities between the two groups were investigated to ascertain the efficacy of immunotherapy. Lastly, the functional analysis of the key risk gene MRAS was carried out via in vitro experiments and a pan-cancer analysis and potential small molecule drugs that may target MRAS were screened through molecular docking. Results Based on seven mitophagy-related prognostic gene signatures, osteosarcoma patients were stratified into high- and low-risk categories. The predictive model exhibited strong prognostic capability, as evidenced by Kaplan-Meier analysis, time-dependent AUC, and Nomogram. Notably, compared to the low-risk group, individuals in the high-risk group exhibited lower stromal, immune, and estimate scores.The infiltration of immune cells in high-risk group decreased. Further evidence supporting MRAS's protective role against osteosarcoma was shown in vitro, where upregulating its expression could suppress the proliferation, migration, and invasion of osteosarcoma cells while stimulating their apoptosis. Pan-cancer analysis further demonstrated its role in a variety of tumors. Conclusion This study identified a mitophagy-related prognostic signature and elucidated the impact of MRAS on osteosarcoma cells. Consequently, it opened up fresh avenues for clinical prognosis prediction and established a basis for precision therapy in osteosarcoma.

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“…Several studies have demonstrated that HuR regulates mRNA expression either by stabilizing messages or by influencing their translation [ 30 , 31 , 32 ]. For instance, HuR bound to the 3′UTR of RAB5C, increasing RAB5C mRNA stability [ 33 ]. HuR affects FGFRL1 expression by binding to and stabilizing FGFRL1 mRNA [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

HuR Promotes the Differentiation of Goat Skeletal Muscle Satellite Cells by Regulating Myomaker mRNA Stability

Sun

Zhan

Zhao

et al. 2023

IJMS

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Human antigen R (HuR) is an RNA-binding protein that contributes to a wide variety of biological processes and diseases. HuR has been demonstrated to regulate muscle growth and development, but its regulatory mechanisms are not well understood, especially in goats. In this study, we found that HuR was highly expressed in the skeletal muscle of goats, and its expression levels changed during longissimus dorsi muscle development in goats. The effects of HuR on goat skeletal muscle development were explored using skeletal muscle satellite cells (MuSCs) as a model. The overexpression of HuR accelerated the expression of myogenic differentiation 1 (MyoD), Myogenin (MyoG), myosin heavy chain (MyHC), and the formation of myotubes, while the knockdown of HuR showed opposite effects in MuSCs. In addition, the inhibition of HuR expression significantly reduced the mRNA stability of MyoD and MyoG. To determine the downstream genes affected by HuR at the differentiation stage, we conducted RNA-Seq using MuSCs treated with small interfering RNA, targeting HuR. The RNA-Seq screened 31 upregulated and 113 downregulated differentially expressed genes (DEGs) in which 11 DEGs related to muscle differentiation were screened for quantitative real-time PCR (qRT-PCR) detection. Compared to the control group, the expression of three DEGs (Myomaker, CHRNA1, and CAPN6) was significantly reduced in the siRNA-HuR group (p < 0.01). In this mechanism, HuR bound to Myomaker and increased the mRNA stability of Myomaker. It then positively regulated the expression of Myomaker. Moreover, the rescue experiments indicated that the overexpression of HuR may reverse the inhibitory impact of Myomaker on myoblast differentiation. Together, our findings reveal a novel role for HuR in promoting muscle differentiation in goats by increasing the stability of Myomaker mRNA.

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RAB5C, a new mRNA binding target of HuR, regulates breast cancer cell proliferation

Cited by 4 publications

References 19 publications

Rare HER2 L796P missense mutation promotes the growth and oncogenic signaling in breast cancer cells

Rare HER2 L796P missense mutation promotes the growth and oncogenic signaling in breast cancer cells

Identification of a novel mitophagy-related signature for predicting clinical prognosis and immunotherapy of osteosarcoma

HuR Promotes the Differentiation of Goat Skeletal Muscle Satellite Cells by Regulating Myomaker mRNA Stability

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