Dataset Information

Heterogeneous nuclear ribonucleoprotein A2/B1 is a negative regulator of human breast cancer metastasis by maintaining the balance of multiple genes and pathways.

ABSTRACT:

Background

Heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1 is an important RNA-binding protein that affects the RNA processing, splicing, transport and stability of many genes. hnRNPA2/B1 is expressed during proliferation and metastasis of various cancer types and promotes such processes. However, the precise role and mechanism of hnRNPA2/B1 in breast cancer remain unclear.

Methods

The association of hnRNPA2/B1 with breast cancer metastasis was assessed using tissue chips, mouse models and publicly available data. The role and mechanism of hnRNPA2/B1 in breast cancer metastasis were studied in cell lines and mouse models.

Findings

In contrast to other cancer research findings, hnRNPA2/B1 expression was negatively correlated with breast cancer metastasis. hnRNPA2/B1 inhibited MDA-MB-231 triple-negative breast cancer (TNBC) cell metastasis in vitro and in vivo. hnRNPA2/B1 knockout activated ERK-MAPK/Twist and GR-beta/TCF4 pathways but inhibited STAT3 and WNT/TCF4 signalling pathways. Profilin 2 (PFN2) promoted breast cancer cell migration and invasion, whereas hnRNPA2/B1 bound directly to the UAGGG locus in the 3'-untranslated region of PFN2 mRNA and reduced the stability of PFN2 mRNA.

Interpretation

Our data supported the role of hnRNPA2/B1 in tumour metastasis risk and survival prediction in patients with breast cancer. The inhibitory role of hnRNPA2/B1 in metastasis was a balance of downstream multiple genes and signalling pathways. PFN2 downregulation by hnRNPA2/B1 might partly explain the inhibitory mechanism of hnRNPA2/B1 in breast cancer metastasis. Therefore, hnRNPA2/B1 might be used as a new prognostic biomarker and valuable molecular target for breast cancer treatments.

SUBMITTER: Liu Y

PROVIDER: S-EPMC6948170 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Publications

Heterogeneous nuclear ribonucleoprotein A2/B1 is a negative regulator of human breast cancer metastasis by maintaining the balance of multiple genes and pathways.

Liu Yu Y Li Huan H Liu Fan F Gao Li-Bin LB Han Rong R Chen Chen C Ding Xue X Li Shuang S Lu Kun K Yang Ling L Tian Hui-Min HM Chen Bin-Bin BB Li Xiao X Xu Dong-Hui DH Deng Xiao-Ling XL Shi Song-Lin SL

EBioMedicine 20200103

<h4>Background</h4>Heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1 is an important RNA-binding protein that affects the RNA processing, splicing, transport and stability of many genes. hnRNPA2/B1 is expressed during proliferation and metastasis of various cancer types and promotes such processes. However, the precise role and mechanism of hnRNPA2/B1 in breast cancer remain unclear.<h4>Methods</h4>The association of hnRNPA2/B1 with breast cancer metastasis was assessed using tissue chips, m ...[more]

PMID: 31901866

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Project description:ObjectivesTongue squamous cell carcinoma (TSCC) is a common cancer in the oral and maxillofacial region, which seriously endangers people's life and health.Heterogeneous nuclear ribonucleoprotein A2/B1(hnRNP A2/B1) is an RNA-binding protein that regulates the expression of a variety of genes and participates in the occurrence and development of a variety of cancers. This study aims to investigate the role of hnRNP A2/B1 in TSCC progression.MethodsThe differential expression of hnRNP A2/B1 in oral squamous cell carcinoma (OSCC) and normal oral mucosa cells and tissues was analyzed based on the gene expression profiles of GSE146483 and GSE85195 in the Gene Expression Omnibus (GEO) database. The correlation between hnRNP A2/B1 expression and disease-free survival of TSCC patients was analyzed based on TSCC related chip of GSE4676. TSCC cancer and paracancerous tissue samples of 30 patients were collected in Hunan Cancer Hospital from July to December 2021. Real-time RT-PCR and Western blotting were used to verify the mRNA and protein expression of hnRNP A2/B1 in TSCC patients'samples, respectively. Human TSCC Tca-8113 cells were transfected with hnRNP A2/B1 empty vector (a sh-NC group), knockdown plasmid (a sh-hnRNP A2/B1 group), empty vector overexpression plasmid (an OE-NC group) and overexpression plasmid (an OE-hnRNP A2/B1 group), respectively. The knockdown or overexpression efficiency of hnRNP A2/B1 was detected by Western blotting. The proliferation activity of Tca-8113 cells was detected by cell counting kit-8 (CCK-8), and the apoptosis rate of Tca-8113 cells was detected by flow cytometry.ResultsBased on the analysis of OSCC-related chips of GSE146483 and GSE85195 in the GEO database, it was found that hnRNP A2/B1 was differentially expressed in the OSCC and normal oral mucosa cells and tissues (all P<0.01). Meanwhile, the analysis of TSCC related chip GSE4676 confirmed that the expression of hnRNP A2/B1 was negatively correlated with the disease-free survival of TSCC patients (P=0.006). The results of real-time RT-PCR and Western blotting showed that the relative expression levels of hnRNP A2/B1 mRNA and protein in TSCC tissues were significantly up-regulated compared with those in adjacent tissues (all P<0.01). The results of Western blotting showed that the expression level of hnRNP A2/B1 in Tca-8113 cells was significantly inhibited or promoted after knockdown or overexpression of hnRNP A2/B1 (all P<0.01). The results of CCK-8 and flow cytometry showed that inhibition of hnRNP A2/B1 expression in Tca-8113 cells reduced cell proliferation activity (P<0.05) and increased cell apoptic rate (P<0.01). Overexpression of hnRNP A2/B1 in Tca-8113 cells significantly increased cell proliferation (P<0.05) and decreased cell apoptosis (P<0.01).ConclusionsHnRNP A2/B1 is a key factor regulating the proliferation and apoptosis of TSCC cells. Inhibition of hnRNP A2/B1 expression can reduce the proliferation activity of TSCC cells and promote the apoptosis of TSCC cells.

Project description:Background and objectivePostoperative neurocognitive dysfunction (PND) occurs in up to 54% of older patients, giving rise to the heavy psychological and economic burdens to patients and society. To date, the development of PND biomarkers remains a challenge. Heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2/B1) is an RNA-binding protein whose prion-like structure is prone to mutation and hence leads to neurodegenerative diseases, but its expression changes in PND remains unclear. Here, we detect the preoperative hnRNPA2/B1 level in patients with PND, and to explore its value in the prediction and diagnosis of PND.MethodsThe study included 161 elderly patients undergoing lumbar decompression and fusion in Nankai University Affinity the Third Central Hospital from September 2021 to July 2022. Neuropsychological and psychometric evaluations were performed before surgery, 1 week and 3 months after surgery to diagnose the occurrence of PND, then the peripheral blood was collected from patients before induction of anesthesia. The concentration in plasma of hnRNPA2/B1 and amyloid-β 42 were determined by enzyme-linked immunosorbent assay. The median fluorescence intensity and mRNA levels of hnRNPA2/B1 in peripheral blood mononuclear cells was detected by indirect intracellular staining flow cytometry and quantitative real-time PCR, respectively.ResultsThe preoperative hnRNPA2/B1 level in patients with PND was higher both in short-time and long-time follow-up. We found significantly higher concentrations of hnRNPA2/B1 in PND at 7 days after surgery (median, 72.26 pg/mL vs. 54.95 pg/mL, p = 0.022) compared with patients without PND, and so as 3 months after surgery (median, 102.93 pg/mL vs. 56.38 pg/mL, p = 0.012). The area under the curve (AUC) was predicted to be 0.686 at 7 days after surgery and 0.735 at 3 months. In addition, when combining several clinical information, the diagnostic efficiency of hnRNPA2/B1 for PND could further increase (AUC, 0.707 at 7 days, 0.808 at 3 months).ConclusionBased on the findings reported here, hnRNPA2/B1 may serve as a new and powerful predictive biomarker to identify elderly patients with PND.

Dataset Information

Heterogeneous nuclear ribonucleoprotein A2/B1 is a negative regulator of human breast cancer metastasis by maintaining the balance of multiple genes and pathways.

Background

Methods

Findings

Interpretation

Publications

Heterogeneous nuclear ribonucleoprotein A2/B1 is a negative regulator of human breast cancer metastasis by maintaining the balance of multiple genes and pathways.

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