C1QBP Negatively Regulates the Activation of Oncoprotein YBX1 in the Renal Cell Carcinoma As Revealed by Interactomics Analysis

Wang, Yong; Yue, Dan; Xiao, Mingming; Qi, Can; Chen, Yajing; Sun, Duxin; Zhang, Ning; Chen, Ruibing

doi:10.1021/pr500847p

Cited by 31 publications

(29 citation statements)

References 36 publications

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“…Our results revealed C1QBP as another factor that could interact with and influence the nuclear translocation of YBX1. This is consistent with their expression pattern showing the expression of C1QBP is negatively correlated with YBX1 nuclear localization in RCC samples [33]. Importantly, our finding that C1QBP might function through YBX1 to modulate AR expression provides a good model of how C1QBP/YBX1 might influence the RCC cell invasion.…”

Section: Discussionsupporting

confidence: 89%

C1QBP Regulates YBX1 to Suppress the Androgen Receptor (AR)-Enhanced RCC Cell Invasion

et al. 2017

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Early studies suggested that the androgen receptor (AR) might play important roles to promote the renal cell carcinoma (RCC) progression; however, the detailed mechanisms remain unclear. Here we demonstrated the higher YBX1 expression with lower C1QBP expression in human RCC clinical tissues, and the intensity of C1QBP was negatively correlated with the YBX1 nuclear expression. Mechanism dissection found C1QBP could interact with YBX1 to suppress the YBX1 activation via altering the YBX1 phosphorylation and nuclear translocation in RCC cells. The consequences of such suppression of YBX1 might then result in suppressing the RCC cell migration and invasion that involved altering the AR-modulated MMP9 signals. Interruption of this newly identified C1QBP → YBX1 → AR → MMP9-suppressed RCC cell invasion pathway via targeting YBX1 or AR partially reversed the RCC cell invasion. Importantly, results from in vivo mouse model with orthotopic implantation of RCC OSRC2 cells into the left renal capsule also confirmed in vitro cell line studies showing targeting YBX1 could suppress RCC cell invasion via regulation of AR/MMP9 signals. Collectively, these data suggest that C1QBP could regulate YBX1 to suppress the AR-enhanced RCC cell invasion. Targeting this newly identified C1QBP/YBX1/AR/MMP9 signal pathway may provide a new potential therapy to better suppress RCC metastasis.

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Section: Discussionsupporting

confidence: 89%

C1QBP Regulates YBX1 to Suppress the Androgen Receptor (AR)-Enhanced RCC Cell Invasion

et al. 2017

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“…Among the 13 identified survival-associated SFs, HNRNPU, PTBP1, and YBX1 have already been revealed in several RCC-related pathways based on previous studies. [55][56][57] These results suggested that our analyses were partly in accordance with previous research. 53 Besides, in vitro and in vivo studies have revealed that PTBP1 could promote tumor angiogenesis and distal metastasis via activating the hypoxia-inducible factor-1α pathway, indicating its important prognostic role in RCC.…”

Section: Discussionsupporting

confidence: 92%

Identification of novel prognostic alternative splicing signature in papillary renal cell carcinoma

Duan

Zhang

2019

J of Cellular Biochemistry

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Papillary renal cell carcinoma (pRCC) is a heterogeneous disease containing multifocal or solitary tumors with an aggressive phenotype. Increasing evidence has indicated the involvement of aberrant splicing variants in renal cell cancer, while systematic profiling of aberrant alternative splicing (AS) in pRCC was lacking and largely unknown. In the current study, comprehensive profiling of AS events were performed based on the integration of pRCC cohort from the Cancer Genome Atlas database and SpliceSeq software. With rigorous screening and univariate Cox analysis, a total of 2077 prognoses AS events from 1642 parent genes were identified. Then, stepwise least absolute shrinkage and selection operator method‐penalized Cox regression analyses with 10‐fold cross‐validation followed by multivariate Cox regression were used to construct the prognostic AS signatures within each AS type. And a final 21 AS event‐based signature was proposed which showed potent prognostic capability in stratifying patients into low‐ and high‐risk subgroups (P < .0001). Furthermore, time‐dependent receiver operating characteristics curves confirmed that the final AS signature was effective and robust in predicting overall survival for pRCC patients with the area under the curve above 0.9 from 1 to 5 years. In addition, splicing correlation network was built to uncover the potential regulatory pattern among prognostic splicing factors and candidate AS events. Besides, gene set enrichment analysis revealed the involvement of these candidates AS events in tumor‐related pathways including extracellular matrix organization, oxidative phosphorylation, and P53 signaling pathways. Taken together, our results could contribute to elucidating the underlying mechanism of AS in the oncogenesis process and broaden the novel field of prognostic and clinical application of molecule‐targeted approaches in pRCC.

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“…But it has also been documented that C1QBP is significantly decreased in human cervical squamous cell carcinoma tissues relative to normal cervix tissues and inhibits viability, migration and proliferation of cervical squamous cells carcinoma via the p38 MAPK signaling pathway 9 . Consistent with the finding in cervical squamous cell carcinoma, our study 10 shows that the level of C1QBP in the renal carcinoma tissues is significantly lower than that in the adjacent normal tissues, and the expression of C1QBP could be used as an independent prognostic maker for cancer progression in the renal cell carcinoma (RCC) patients. In a word, it is tissue specificity of C1QBP expression and C1QBP appears to be tumor suppresser in RCC.…”

Section: Introductionsupporting

confidence: 89%

“…Because of the complicated mechanisms of tumor development, there’s much to explore for development of potential targeted therapies for RCC as well as discovery of new biomarkers for RCC staging and prognosis. In the previous study 10 , immunohistochemistry and western blotting are used to study the expression of C1QBP in renal carcinoma tissue and cells, the expression of C1QBP in renal carcinoma tissue is lower compared with para-carcinoma tissue. We further examined the potential biological consequence of a lowered expression of C1QBP in this study.…”

Section: Discussionmentioning

confidence: 99%

C1QBP suppresses cell adhesion and metastasis of renal carcinoma cells

Wang

et al. 2017

Sci Rep

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Complement component 1q subcomponent binding protein (C1QBP) is a ubiquitously expressed cellular protein and can be upregulated or activated in a variety of malignant tumors, including those from thyroid, colon and breast, but its role remains unclear in renal cell carcinoma (RCC). In this study, C1QBP knockdown in RCC cell influenced expression of multiple genes associated with cell adhesion, among which L1 cell adhesion molecule (L1CAM) was significantly higher upon a reduction of C1QBP. In turn, cell adhesion and invasion abilities were significantly increased with increased metastasis to lung and liver in vivo. C1QBP may regulate RCC cell adhesion and invasion through influencing the p-GSK3/β-Catenin/L1CAM expression. Over all, our study demonstrated that C1QBP could regulate RCC metastasis by regulating the GSK3/β-Catenin/L1CAM signaling pathway.

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C1QBP Negatively Regulates the Activation of Oncoprotein YBX1 in the Renal Cell Carcinoma As Revealed by Interactomics Analysis

Cited by 31 publications

References 36 publications

C1QBP Regulates YBX1 to Suppress the Androgen Receptor (AR)-Enhanced RCC Cell Invasion

C1QBP Regulates YBX1 to Suppress the Androgen Receptor (AR)-Enhanced RCC Cell Invasion

Identification of novel prognostic alternative splicing signature in papillary renal cell carcinoma

C1QBP suppresses cell adhesion and metastasis of renal carcinoma cells

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