CSE1L, DIDO1 and RBM39 in colorectal adenoma to carcinoma progression

Sillars-Hardebol, Anke H.; Carvalho, Beatriz; Beliën, Jeroen A.M.; Wit, Meike de; Diemen, Pien M. Delis-van; Tijssen, Marianne; Wiel, Mark A. van de; Pontén, Fredrik; Meijer, Gerrit A.; Fijneman, Remond J.A.

doi:10.1007/s13402-012-0088-2

“…In colon cancer cell lines, NR2C2 is required for cell survival and its inhibition induces cell death (McNew et al., ; Singh et al., ). DIDO1 regulates embryonic stem cell renewal (Liu et al., ) and is upregulated in melanoma tissues and cell lines as well as colorectal tumors (Braig & Bosserhoff, ; Sillars‐Hardebol et al., ), although in the latter, there was no correlation to gene copy number and DIDO1 was suggested to be a passenger on the common 20q duplication seen in CRC. The remaining four have no known cancer‐related function ( KIAA1109 , GPHN , GPR25 , ZNF462 ).…”

Section: Discussionmentioning

confidence: 99%

Exome sequencing in 51 early onset non‐familial CRC cases

Thutkawkorapin

¹

,

Lindblom

²

,

Tham

³

2019

Molec Gen & Gen Med

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Background Colorectal cancer ( CRC ) cases with an age of onset <40 years suggests a germline genetic cause. In total, 51 simplex cases were included to test the hypothesis of CRC as a mendelian trait caused by either heterozygous autosomal dominant or bi‐allelic autosomal recessive pathogenic variants. Methods The cohort was whole exome sequenced ( WES ) at 100× coverage. Both a dominant‐ and recessive model were used for searching predisposing genetic factors. In addition, we assayed recessive variants of potential moderate risk that were enriched in our young‐onset CRC cohort. Variants were filtered using a candidate cancer gene list or by selecting variants more likely to be pathogenic based on variant type (e.g., loss‐of‐function) or allele frequency. Results We identified one pathogenic variant in PTEN in a patient subsequently confirmed to have a hereditary hamartoma tumor syndrome (Cowden syndrome) and one patient with a pathogenic heterozygous variant in PMS 2 that was originally not identified by WES due to low quality reads resulting from pseudogenes. In addition, we identified three heterozygous candidate missense variants in known cancer susceptibility genes ( BMPR 1A , BRIP 1 , and SRC ) , three truncating variants in possibly novel cancer genes ( CLSPN , SEC 24B , SSH 2 ) and four candidate missense variants in ACACA , NR 2C2 , INPP 4A, and DIDO 1 . We also identify five possible autosomal recessive candidate genes: ATP 10B , PKHD 1 , UGGT 2 , MYH 13 , TFF 3 . Conclusion Two clear pathogenic variants were identified in patients that had not been identified clinically. Thus, the chance of detecting a hereditary cancer syndrome in patients with CRC at young age but without family history is 2/51 (4%) and therefore the clinical benefit of genetic testing in this patient group is low. Of note, using stringent filtering, we have identified a total of ten candidate heterozygous variants and five possibly biallelic autosomal recessive candidate genes that warrant further study.

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“…23 Interestingly, CAPER expression was also recently shown to be upregulated in human colorectal adenomas and carcinomas. 25 The expression of CAPER was reported to affect the survival of colorectal cancer cells. 26 Indeed, knockdown of CAPER expression markedly reduced the viability of human colorectal cancer cell lines under both normal culture conditions and upon 5-Fluorodeoxyuridine (5FU)-induced cytotoxicity, suggesting a potential role of CAPER in apoptosis and/or cell senescence.…”

Section: Discussionmentioning

confidence: 99%

CAPER, a novel regulator of human breast cancer progression

Mercier

¹

,

Gonzales

²

,

Quann

³

et al. 2014

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“…RBM39 function has been linked to a number of cancers and malignant progression , and the RBM39-interacting proteins in particular environments determine the anti-or pro-oncogenic activity of RBM39. RBM39 expression is upregulated in small-cell lung and breast cancers, colorectal adenomas and carcinomas (Bangur et al, 2002;Mercier et al, 2009;Chai et al, 2014;Sillars-Hardebol, Carvalho, Belië n et al, 2012). Knockdown of RBM39 expression suppresses the oncogenic activity of the NF-Bv v-Rel protein in lymphocytes (Dutta et al, 2008) and the proliferation of ER-positive human breast cancer cells.…”

Section: Introductionmentioning

confidence: 99%

UHM–ULM interactions in the RBM39–U2AF65 splicing-factor complex

Stepanyuk

¹

,

Serrano

²

,

Peralta

³

et al. 2016

Acta Crystallogr D Struct Biol

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RNA-binding protein 39 (RBM39) is a splicing factor and a transcriptional coactivator of estrogen receptors and Jun/AP-1, and its function has been associated with malignant progression in a number of cancers. The C-terminal RRM domain of RBM39 belongs to the U2AF homology motif family (UHM), which mediate protein-protein interactions through a short tryptophancontaining peptide known as the UHM-ligand motif (ULM). Here, crystal and solution NMR structures of the RBM39-UHM domain, and the crystal structure of its complex with U2AF65-ULM, are reported. The RBM39-U2AF65 interaction was confirmed by co-immunoprecipitation from human cell extracts, by isothermal titration calorimetry and by NMR chemical shift perturbation experiments with the purified proteins. When compared with related complexes, such as U2AF35-U2AF65 and RBM39-SF3b155, the RBM39-UHM-U2AF65-ULM complex reveals both common and discriminating recognition elements in the UHM-ULM binding interface, providing a rationale for the known specificity of UHM-ULM interactions. This study therefore establishes a structural basis for specific UHM-ULM interactions by splicing factors such as U2AF35, U2AF65, RBM39 and SF3b155, and a platform for continued studies of intermolecular interactions governing disease-related alternative splicing in eukaryotic cells.

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CSE1L, DIDO1 and RBM39 in colorectal adenoma to carcinoma progression

Cited by 29 publications

References 43 publications

Exome sequencing in 51 early onset non‐familial CRC cases

Exome sequencing in 51 early onset non‐familial CRC cases

CAPER, a novel regulator of human breast cancer progression

UHM–ULM interactions in the RBM39–U2AF65 splicing-factor complex

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