An ERCC1 splicing variant involving the 5′-UTR of the mRNA may have a transcriptional modulatory function

Yu, Jing; Thornton, Keith; Guo, Yi; Kotz, Herbert L.; Reed, Eddie

doi:10.1038/sj.onc.1204977

Cited by 22 publications

(21 citation statements)

References 13 publications

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“…Another smaller product is observed whose size is consistent with that of a 42 bp deletion from the 206 bp band. It has been suggested that ovarian cancer specimens that express high overall levels of ERCC1 transcripts express the deleted transcript as well as the undeleted transcript, while in specimens expressing low overall levels of ERCC1 transcript, the deleted transcript is absent (Yu et al, 2001). However, in each of our ovarian cell lines, some of which are cisplatin sensitive, both of these PCR products are present.…”

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confidence: 72%

“…Indeed all the cell lines and tissues examined express the undeleted and deleted transcripts at similar ratios (1.2-1.6 : 1). These data make it difficult to maintain that the deleted transcript is correlated with high levels of ERCC1 expression, as suggested by Yu et al (2001), and therefore its significance remains unclear. In addition, the deleted transcript is clearly present in normal ovary tissue and indeed other tissues, which PEO23 and PEA2 are cisplatin-resistant derivatives of PEO14 and PEA1, respectively.…”

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confidence: 94%

“…A 42 bp sequence, thought to contain a binding site for a transcriptional repressor, has been identified in exon 1 of the human ERCC1 gene (Yu et al, 2001). Loss of this sequence during splicing produces a shorter transcript that was reported to be correlated with higher levels of ERCC1 mRNA in ovarian cancer specimens.…”

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confidence: 99%

“…It has been suggested (Yu et al, 2001;Li et al, 2004) that the function of the deleted sequence may be as a transcriptional regulator, as evidenced by luciferase assays and EMSA studies. However, the authors fail to explain how exclusion of this sequence in an alternative transcript, as observed by RT-PCR, would have any effect on transcription, since the difference is seen at the post-transcriptional level.…”

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confidence: 99%

“…The RT-PCR was designed to amplify the ERCC1 exon 1 to exon 2 region, containing the 42 bp sequence previously identified as a possible regulator of transcription (Yu et al, 2001;Li et al, 2004). A 206 bp band is seen in all samples, which represents PCR product amplified from the known human ERCC1 cDNA sequence.…”

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confidence: 99%

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Expression of a splicing variant in the 5′-UTR of the human ERCC1 gene is not cancer related

2005

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confidence: 72%

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confidence: 94%

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confidence: 99%

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confidence: 99%

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confidence: 99%

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Expression of a splicing variant in the 5′-UTR of the human ERCC1 gene is not cancer related

2005

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Regulation of DNA repair gene expression in human cancer cell lines

McGurk

Cummings

Köberle

et al. 2005

J of Cellular Biochemistry

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Although most advanced cancers are incurable, the majority of testicular germ cell tumors can be cured using cisplatin-based combination chemotherapy. The nucleotide excision repair (NER) pathway removes most DNA adducts produced by cisplatin, and the low levels of NER in testis tumor cells may explain why these cancers are curable. Three NER proteins: ERCC1, XPF, and XPA, are present at low levels in testis tumor cell lines, and addition of these proteins to protein extracts of testis tumor cells increases their in vitro DNA repair capacity to normal levels. The aim of this study was to identify the mechanism responsible for the low levels of these DNA repair proteins. The levels of the mRNA transcripts for ERCC1, XPF, and XPA were measured in a panel of 14 different human cancer cell lines, using real-time PCR. Three ERCC1 splice variants were identified and quantitated. Three alternative transcription start points (TSPs) were identified for ERCC1 but none were testis-specific. The significantly lower levels of ERCC1, XPF, and XPA protein in testis tumor cell lines cannot be explained solely by differences in transcriptional efficiency or mRNA stability. For ERCC1, post-transcriptional control by alternative splicing does not account for the testis-specific low levels of protein expression. Pulse-chase experiments showed that the half-life of ERCC1 protein in a testis tumor cell line was not significantly different to that in a prostate cancer cell line. Taken together, these results suggest that constitutive levels of these DNA repair proteins are controlled at the level of translation.

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RNA splicing alteration in the response to platinum chemotherapy in ovarian cancer: A possible biomarker and therapeutic target

Pellarin

Belletti

Baldassarre

2020

Medicinal Research Reviews

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Since its discovery, alternative splicing has been recognized as a powerful way for a cell to amplify the genetic information and for a living organism to adapt, evolve, and survive. We now know that a very high number of genes are regulated by alternative splicing and that alterations of splicing have been observed in different types of human diseases, including cancer. Here, we review the accumulating knowledge that links the regulation of alternative splicing to the response to chemotherapy, focusing our attention on ovarian cancer and platinum‐based treatments. Moreover, we discuss how expanding information could be exploited to identify new possible biomarkers of platinum response, to better select patients, and/or to design new therapies able to overcome platinum resistance.

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An ERCC1 splicing variant involving the 5′-UTR of the mRNA may have a transcriptional modulatory function

Cited by 22 publications

References 13 publications

Expression of a splicing variant in the 5′-UTR of the human ERCC1 gene is not cancer related

Expression of a splicing variant in the 5′-UTR of the human ERCC1 gene is not cancer related

Regulation of DNA repair gene expression in human cancer cell lines

RNA splicing alteration in the response to platinum chemotherapy in ovarian cancer: A possible biomarker and therapeutic target

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