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Identification of RNA-binding protein SNRPA1 for prognosis in prostate cancer.

ABSTRACT: Prostate cancer is one of the deadliest cancers in men. RNA-binding proteins play a critical role in human cancers; however, whether they have a significant effect on the prognosis of prostate cancer has yet to be elucidated. In the present study, we performed a comprehensive analysis of RNA sequencing and clinical data from the Cancer Genome Atlas dataset and obtained differentially expressed RNA-binding proteins between prostate cancer and benign tissues. We constructed a protein-protein interaction network and Cox regression analyses were conducted to identify prognostic hub RNA-binding proteins. SNRPA1 was associated with the highest risk of poor prognosis and was therefore selected for further analysis. SNRPA1 expression was positively correlated with Gleason score and pathological TNM stage in prostate cancer patients. Furthermore, the expression profile of SNRPA1 was validated using the Oncomine, Human Protein Atlas, and Cancer Cell Line Encyclopedia databases. Meanwhile, the prognostic profile of SNRPA1 was successfully verified in GSE70769. Additionally, the results of molecular experiments revealed the proliferative role of SNRPA1 in prostate cancer cells. In summary, our findings evidenced a relationship between RNA-binding proteins and prostate cancer and indicated the prognostic significance of SNRPA1 in prostate cancer.

SUBMITTER: Yuan P

PROVIDER: S-EPMC7880319 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Identification of RNA-binding protein SNRPA1 for prognosis in prostate cancer.

Yuan Penghui P Ling Le L Gao Xintao X Sun Taotao T Miao Jianping J Yuan Xianglin X Liu Jihong J Wang Zhihua Z Liu Bo B

Aging 20210115 2

Prostate cancer is one of the deadliest cancers in men. RNA-binding proteins play a critical role in human cancers; however, whether they have a significant effect on the prognosis of prostate cancer has yet to be elucidated. In the present study, we performed a comprehensive analysis of RNA sequencing and clinical data from the Cancer Genome Atlas dataset and obtained differentially expressed RNA-binding proteins between prostate cancer and benign tissues. We constructed a protein-protein inter ...[more]

PMID: 33460399

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Project description:BackgroundProstate cancer is one of the most common malignant cancers with the second highest global rate of mortality in men. During the early stages of disease progression, tumour growth is local and androgen-dependent. Despite treatment, a large percentage of patients develop androgen-independent prostate cancer, which often results in metastases, a leading cause of mortality in these patients. Our previous work on the RNA-binding protein Staufen1 demonstrated its novel role in cancer biology, and in particular rhabdomyosarcoma tumorigenesis. To build upon this work, we have focused on the role of Staufen1 in other forms of cancer and describe here the novel and differential roles of Staufen1 in prostate cancer.MethodsUsing a cell-based approach, three independent prostate cancer cell lines with different characteristics were used to evaluate the expression of Staufen1 in human prostate cancer relative to control prostate cells. The functional impact of Staufen1 on several key oncogenic features of prostate cancer cells including proliferation, apoptosis, migration and invasion were systematically investigated.ResultsWe show that Staufen1 levels are increased in all human prostate cancer cells examined in comparison to normal prostate epithelial cells. Furthermore, Staufen1 differentially regulates growth, migration, and invasion in the various prostate cancer cells assessed. In LNCaP prostate cancer cells, Staufen1 regulates cell proliferation through mTOR activation. Conversely, Staufen1 regulates migration and invasion of the highly invasive, bone metastatic-derived, PC3 prostate cells via the activation of focal adhesion kinase.ConclusionsCollectively, these results show that Staufen1 has a direct impact in prostate cancer development and further demonstrate that its functions vary amongst the prostate cancer cell types. Accordingly, Staufen1 represents a novel target for the development of much-needed therapeutic strategies for prostate cancer.

Project description:BackgroundTo date, breast cancer remains the primary cause of tumor-related death among women, even though some leap-type developments of oncology have been done to slash the mortality. Considering the tumor heterogeneity and individual variation, the more reliable biomarkers are required to be identified for supporting the development of precision medicine in breast cancer.MethodsBased on the TCGA-BRCA and METABRIC databases, the differently expressed RNA binding proteins (RBPs) between tumor and normal tissues were investigated. In this study, we focused on the communal differently expressed RBPs in four subtypes of breast cancer. Lasso-penalized Cox analysis, Stepwise-multivariate Cox analysis and Kaplan-Meier survival curve were performed to identify the hub RBP-coding genes in predicting prognosis of breast cancer, and a prognostic model was established. The efficiency of this model was further validated in other independent GSE20685, GSE4922 and FUSCC-TNBC cohorts by calculating the risk score and performing survival analysis, ROC and nomogram. Moreover, pathologic functions of the candidate RBPs in breast cancer were explored using some routine experiments in vitro, and the potential compounds targeting these RBPs were predicted by reviewing the Comparative Toxicogenomics Database.ResultsHere, we identified 62 RBPs which were differently expressed between the tumor and normal tissues. Thereinto, three RBPs (MRPL12, MRPL13 and POP1) acted as independent risk factors, and their expression pattern also correlated with poor prognosis of patients. A prognostic model, built with these 3-RBPs, possessed statistical significance to predict the survival probability of patients with breast cancer. Furthermore, experimental validations showed that down-regulating the expression of endogenous MRPL12, MRPL13 or POP1 could dramatically suppress the cellular viability and migration of breast cancer cells in vitro. Besides, some compounds (such as the Acetaminophen, Urethane and Tunicamycin) were predicted for curing breast cancer via targeting MRPL12, MRPL13 and POP1 simultaneously.ConclusionThis study identified and established a 3-RBPs-based signature and nomogram for predicting the survival probability of patients with breast cancer. MRPL12, MRPL13 and POP1 might act as oncogenes in maintaining cellular viability and accelerating metastasis of breast cancer cells, implying the possibility of which to be designed as biomarkers and/or therapeutic targets for breast cancer.

Dataset Information

Identification of RNA-binding protein SNRPA1 for prognosis in prostate cancer.

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Identification of RNA-binding protein SNRPA1 for prognosis in prostate cancer.

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