The Impacts of ERCC1 Gene Exon VIII Alternative Splicing on Cisplatin-Resistance in Ovarian Cancer Cells

Sun, Yuhan; Li, Tiyuan; Ma, Kewei; Tian, Zhongkai; Zhu, Ying; Chen, Fuqiang; Hu, Gang

doi:10.1080/07357900902744536

Cited by 6 publications

(8 citation statements)

References 0 publications

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“…[29][30][31] We could not find any evidence supporting this hypothesis, at least with regards to the DDR-related function of ERCC1 after inducing DNA damage with platinum agents. Cisplatin generates several types of DNA adduct that are processed by distinct DNA repair pathways and differently impact cell survival.…”

Section: Discussioncontrasting

confidence: 46%

“…Another function has nevertheless been suggested for the ERCC1 isoform 203 as a dominant-negative modulator of ERCC1 activity. [29][30][31] We therefore searched for dominant-negative effects of the ERCC1 isoforms toward the active isoform 202. For that purpose, two A549 ERCC1-deficient clones were successively transduced with a lentiviral vector expressing isoform 202, and then additionally with a lentivirus driving the expression of either isoform 201, 203, or 204.…”

Section: Lack Of Dominant-negative Isoformmentioning

confidence: 99%

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ERCC1 function in nuclear excision and interstrand crosslink repair pathways is mediated exclusively by the ERCC1-202 isoform

Friboulet

Postel-Vinay²,

Sourisseau

et al. 2013

Cell Cycle

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Section: Discussioncontrasting

confidence: 46%

Section: Lack Of Dominant-negative Isoformmentioning

confidence: 99%

ERCC1 function in nuclear excision and interstrand crosslink repair pathways is mediated exclusively by the ERCC1-202 isoform

Friboulet

Postel-Vinay²,

Sourisseau

et al. 2013

Cell Cycle

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“…Several reports suggest that alternative splicing of specific genes, such as BRCA1, BRCA2, BARD1, or ERCC1, can impact on the response of cancer cells to PT and some studies also suggest that this correlates with PT resistance in human cancer [23][24][25][26][27][28]. Accordingly, it has been proposed that evaluation of alternative splicing of selected genes could serve as prognostic marker in ovarian cancer [29].…”

Section: Discussionmentioning

confidence: 99%

Splicing factor proline- and glutamine-rich (SFPQ) protein regulates platinum response in ovarian cancer-modulating SRSF2 activity

et al. 2020

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In epithelial ovarian cancer (EOC), response to platinum (PT)-based chemotherapy dictates subsequent treatments and predicts patients' prognosis. Alternative splicing is often deregulated in human cancers and can be altered by chemotherapy. Whether and how changes in alternative splicing regulation could impact on the response of EOC to PT-based chemotherapy is still not clarified. We identified the splicing factor proline and glutamine rich (SFPQ) as a critical mediator of response to PT in an unbiased functional genomic screening in EOC cells and, using a large cohort of primary and recurrent EOC samples, we observed that it is frequently overexpressed in recurrent PT-treated samples and that its overexpression correlates with PT resistance. At mechanistic level, we show that, under PT treatment, SFPQ, in complex with p54 nrb , binds and regulates the activity of the splicing factor SRSF2. SFPQ/p54 nrb complex decreases SRSF2 binding to caspase-9 RNA, favoring the expression of its alternative spliced antiapoptotic form. As a consequence, SFPQ/p54 nrb protects cells from PTinduced death, eventually contributing to chemoresistance. Overall, our work unveils a previously unreported SFPQ/p54 nrb / SRSF2 pathway that in EOC cells plays a central role in regulating alternative splicing and PT-induced apoptosis and that could result in the design of new possible ways of intervention to overcome PT resistance.

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“…Furthermore, the ERCC1 epitopes recognized by the different ERCC1 antibodies are unknown. ERCC1 IHC and qRT-PCR discrepancies could therefore be also related to the presence of different ERCC1 isoforms (32). The antibodies used may be specific to one or several ERCC1 isoforms, whereas qRT-PCR primers designed in this study recognized all ERCC1 isoforms.…”

Section: Discussionmentioning

confidence: 99%

Molecular Characteristics of ERCC1-Negative versus ERCC1-Positive Tumors in Resected NSCLC

Friboulet

Barrios-Gonzales

Commo

et al. 2011

Clinical Cancer Research

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Purpose: Excision repair cross-complementation group 1 (ERCC1) is a protein involved in repair of DNA platinum adducts and stalled DNA replication forks. We and others have previously shown the influence of ERCC1 expression upon survival rates and benefit of cisplatin-based chemotherapy in patients with resected non-small-cell lung cancer (NSCLC). However, little is known about the molecular characteristics of ERCC1-positive and ERCC1-negative tumors.Experimental Design: We took advantage of a cohort of 91 patients with resected NSCLC, for which we had matched frozen and paraffin-embedded samples to explore the comparative molecular portraits of ERCC1-positive and ERCC1-negative tumors of NSCLC. We carried out a global molecular analysis including assessment of ERCC1 expression levels by using both immunohistochemistry (IHC) and quantitative reverse transcriptase PCR (qRT-PCR), genomic instability, global gene and miRNA expression, and sequencing of selected key genes involved in lung carcinogenesis.Results: ERCC1 protein and mRNA expression were significantly correlated. However, we observed several cases with clear discrepancies. We noted that ERCC1-negative tumors had a higher rate of genomic abnormalities versus ERCC1-positive tumors. ERCC1-positive tumors seemed to share a common DNA damage response (DDR) phenotype with the overexpression of seven genes linked to DDR. The miRNA expression analysis identified miR-375 as significantly underexpressed in ERCC1-positive tumors.Conclusions: Our data show inconsistencies in ERCC1 expression between IHC and qRT-PCR readouts. Furthermore, ERCC1 status is not linked to specific mutational patterns or frequencies. Finally, ERCC1-negative tumors have a high rate of genomic aberrations that could consequently influence prognosis in patients with resected NSCLC. Clin Cancer Res; 17(17); 5562-72. Ó2011 AACR.

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The Impacts of ERCC1 Gene Exon VIII Alternative Splicing on Cisplatin-Resistance in Ovarian Cancer Cells

Cited by 6 publications

References 0 publications

ERCC1 function in nuclear excision and interstrand crosslink repair pathways is mediated exclusively by the ERCC1-202 isoform

ERCC1 function in nuclear excision and interstrand crosslink repair pathways is mediated exclusively by the ERCC1-202 isoform

Splicing factor proline- and glutamine-rich (SFPQ) protein regulates platinum response in ovarian cancer-modulating SRSF2 activity

Molecular Characteristics of ERCC1-Negative versus ERCC1-Positive Tumors in Resected NSCLC

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