IGFBP-3 interacts with NONO and SFPQ in PARP-dependent DNA damage repair in triple-negative breast cancer

Silva, Hasanthi C. de; Lin, Mike Z.; Phillips, Leo; Martin, Janet L.; Baxter, Robert C.

doi:10.1007/s00018-019-03033-4

Cited by 68 publications

(50 citation statements)

References 52 publications

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“…Recent studies have determined that the treatment of etoposide to TNBC cell line, HCC1806 and MDA-MB-468 resulted in increased interaction between IGFBP-3 and a DNA/RNA binding protein namely NONO, and its dimerization partner splicing factor proline/glutamine-rich (SFPQ) (de Silva et al, 2019). NONO binding with IGFBP-3 was demonstrated in cell free systems (de Silva et al, 2019). The binding between IGFBP-3, NONO and SFPQ could be blunted by inhibitors of EGFR, gefitinib or with inhibitor of DNA-PK, NU7026 and by PARP inhibitors, veliparib and olaparib.…”

Section: Igfbp-3 Interacts With Egfr and Dna-dependent Protein Kinasementioning

confidence: 93%

“…The binding between IGFBP-3, NONO and SFPQ could be blunted by inhibitors of EGFR, gefitinib or with inhibitor of DNA-PK, NU7026 and by PARP inhibitors, veliparib and olaparib. The above-mentioned inhibitors of EGFR, DNA-PK, and PARP could also reduce the NHEJ activity (de Silva et al, 2019). Long noncoding RNA, LINP1 could also abrogate the interactions between IGFBP-3, NONO, and SFPQ (de Silva et al, 2019).…”

Section: Igfbp-3 Interacts With Egfr and Dna-dependent Protein Kinasementioning

confidence: 99%

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Insulin-Like Growth Factor Binding Protein-3 (IGFBP-3): Unraveling the Role in Mediating IGF-Independent Effects Within the Cell

Shrivastav

Bhardwaj

Pathak

et al. 2020

Front. Cell Dev. Biol.

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Section: Igfbp-3 Interacts With Egfr and Dna-dependent Protein Kinasementioning

confidence: 93%

Section: Igfbp-3 Interacts With Egfr and Dna-dependent Protein Kinasementioning

confidence: 99%

Insulin-Like Growth Factor Binding Protein-3 (IGFBP-3): Unraveling the Role in Mediating IGF-Independent Effects Within the Cell

Shrivastav

Bhardwaj

Pathak

et al. 2020

Front. Cell Dev. Biol.

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“…STAT3 along with NONO confer chemoresistance, which is highly correlated with the DNA repair pathway; previous studies have already revealed that NONO does influence the DNA repair pathway 45 - 47 . Our data partially provide that NONO maybe confer chemoresistance through its DNA repair pathway regulation.…”

Section: Discussionmentioning

confidence: 97%

RNA-binding protein NONO contributes to cancer cell growth and confers drug resistance as a theranostic target in TNBC

Kim

Kang

et al. 2020

Theranostics

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Breast cancer (BC) is one of the most common cancers in women. TNBC (Triple-negative breast cancer) has limited treatment options and still lacks viable molecular targets, leading to poor outcomes. Recently, RNA-binding proteins (RBPs) have been shown to play crucial roles in human cancers, including BC, by modulating a number of oncogenic phenotypes. This suggests that RBPs represent potential molecular targets for BC therapy. Methods: We employed genomic data to identify RBPs specifically expressed in TNBC. NONO was silenced in TNBC cell lines to examine cell growth, colony formation, invasion, and migration. Gene expression profiles in NONO-silenced cells were generated and analyzed. A high-throughput screening for NONO-targeted drugs was performed using an FDA-approved library. Results: We found that the NONO RBP is highly expressed in TNBC and is associated with poor patient outcomes. NONO binds to STAT3 mRNA, increasing STAT3 mRNA levels in TNBC. Surprisingly, NONO directly interacts with STAT3 protein increasing its stability and transcriptional activity, thus contributing to its oncogenic function. Importantly, high-throughput drug screening revealed that auranofin is a potential NONO inhibitor and inhibits cell growth in TNBC. Conclusions: NONO is an RBP upstream regulator of both STAT3 RNA and protein levels and function. It represents an important and clinically relevant promoter of growth and resistance of TNBCs. NONO is also therefore a potential therapeutic target in TNBC.

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“…De Silva et al suggested that inhibiting the expression of LINP1 in TNBC cell lines blocks the interaction between insulin like growth factor binding protein 3 and non-POU domain containing octamer binding-splicing factor proline and glutamine rich, thereby affecting the DNA damage repair of cells. These results suggest that LINP1 affects the chemotherapy sensitivity of TNBC, and may be a therapeutic target for the treatment of TNBC [30]. However, studies on the role of LINP1 in cancer have reported inconsistent results.…”

Section: Discussionmentioning

confidence: 97%

Genome-wide RNA-sequencing dataset reveals the prognostic value and potential molecular mechanisms of lncRNA in non-homologous end joining pathway 1 in early stage Pancreatic Ductal Adenocarcinoma

Shang¹,

Liao²,

Zhu³

et al. 2020

J. Cancer

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Objective: Our current study is to explore the prognostic value and molecular mechanisms underlying the role of lncRNA in non-homologous end joining pathway 1 (LINP1) in early stage pancreatic ductal adenocarcinoma (PDAC). Methods: Genome-wide RNA-seq datasets of 112 early stage PDAC patients were got from The Cancer Genome Atlas and analyzed using multiple online tools. Results: Overall survival in high LINP1 expression patients was shorter than those with low expression (high-LINP1 vs. low-LINP1=481 vs. 592 days, log-rank P=0.0432). The multivariate Cox proportional hazard regression model suggested that high-LINP1 patients had a markedly higher risk of death than low-LINP1 patients (adjusted P=0.004, hazard ratio=2.214, 95% confidence interval=1.283-3.820). Analysis of genome-wide co-expressed genes, screening of differentially expressed genes, and gene set enrichment analysis indicated that LINP1 may be involved in the regulation of cell proliferation-, cell adhesion-and cell cycle-related biological processes in PDAC. Six small-molecule compounds including STOCK1N-35874, fenofibrate, exisulind, NU-1025, vinburnine, and doxylamine were identified as potential LINP1-targeted drugs for the treatment of PDAC. Conclusions: Our study indicated that LINP1 may serve as a prognostic biomarker of early stage PDAC. Analysis of genome-wide datasets led to the elucidation of the underlying mechanisms and identified six potential targeted drugs for the treatment of early PDAC.

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IGFBP-3 interacts with NONO and SFPQ in PARP-dependent DNA damage repair in triple-negative breast cancer

Cited by 68 publications

References 52 publications

Insulin-Like Growth Factor Binding Protein-3 (IGFBP-3): Unraveling the Role in Mediating IGF-Independent Effects Within the Cell

Insulin-Like Growth Factor Binding Protein-3 (IGFBP-3): Unraveling the Role in Mediating IGF-Independent Effects Within the Cell

RNA-binding protein NONO contributes to cancer cell growth and confers drug resistance as a theranostic target in TNBC

Genome-wide RNA-sequencing dataset reveals the prognostic value and potential molecular mechanisms of lncRNA in non-homologous end joining pathway 1 in early stage Pancreatic Ductal Adenocarcinoma

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