Novel RNA variants in colorectal cancers

Hoff, Andreas; Johannessen, Bjarne; Alagaratnam, Sharmini; Zhao, Sen; Nome, Torfinn; Løvf, Marthe; Bakken, Anne Cathrine; Hektoen, Merete; Sveen, Anita; Skotheim, Rolf Inge

doi:10.18632/oncotarget.5500

Cited by 16 publications

(11 citation statements)

References 55 publications

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“…Recently, the importance of CASZ1 in tumorigenesis is becoming increasingly recognized. Aberrant fusion transcript of CASZ1 has been reported in colorectal cancer [ 18 ] and bladder cancer [ 19 ]. CASZ1 is downregulated and functions as a crucial tumor suppressor in neuroblastoma [ 20 , 21 ].…”

Section: Introductionmentioning

confidence: 99%

Downregulation of castor zinc finger 1 predicts poor prognosis and facilitates hepatocellular carcinoma progression via MAPK/ERK signaling

Wang

Yang

Xiao

et al. 2018

J Exp Clin Cancer Res

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BackgroundCastor zinc finger 1 (CASZ1) plays critical roles in various biological processes and pathologic conditions, including cancer. However, the prognostic importance and biologic functions of CASZ1 in hepatocellular carcinoma (HCC) are still unclear.MethodsqRT-PCR, western blot and immunohistochemistry analyses were used to determine CASZ1 expression in HCC samples and cell lines. The clinical significance of CASZ1 was assessed in two independent study cohorts containing 232 patients with HCC. A series of in vitro and in vivo experiments were performed to explore the role and molecular mechanism of CASZ1 in HCC progression.ResultsHere we report that CASZ1 expression was downregulated in HCC tissues and cell lines. Low CASZ1 expression was closely correlated with aggressive clinicopathological features, poor clinical outcomes and early recurrence of HCC patients. Moreover, overexpression of CASZ1 in HCCLM3 cells significantly inhibited cell proliferation, migration, invasion in vitro and tumor growth and metastasis in vivo, whereas silencing CASZ1 significantly enhanced the above abilities of PLC/PRF/5 cells. Further mechanism study indicated that these phenotypic changes were mediated by MAPK/ERK signaling pathway and involved altered expression of MMP2, MMP9 and cyclinD1. Finally, we proved that CASZ1 exerted its tumor-suppressive effect by directly interacting with RAF1 and reducing the protein stability of RAF1.ConclusionsOur study for the first time demonstrated that CASZ1 is a tumor suppressor in HCC, which may serve as a novel prognostic predictor and therapeutic target for HCC patients.Electronic supplementary materialThe online version of this article (10.1186/s13046-018-0720-8) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

Downregulation of castor zinc finger 1 predicts poor prognosis and facilitates hepatocellular carcinoma progression via MAPK/ERK signaling

Wang

Yang

Xiao

et al. 2018

J Exp Clin Cancer Res

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“…Some potential biomarkers in cancers have been identified based on exon microarray or NGS. For example, through the combination of exon microarray and RNA sequencing (RNA-Seq), Hoff et al found that the fusion of VWA2-TCF7L2, DHX35-BPIFA2, and CASZ1-MASP2, as well as some novel transcript structures, may play an important role in CRC [ 13 ]. Compared with NGS, microarray has some obvious shortcomings, including the fact that it cannot detect unknown alterations of genomic structure that might contribute to progression of cancers [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

CBX8 and CD96 Are Important Prognostic Biomarkers of Colorectal Cancer

Song

Tang

et al. 2018

Med Sci Monit

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BackgroundColorectal cancer (CRC) is one of the most common malignancies worldwide, with high morbidity and mortality rates. The purpose of this study was to identify potential biomarkers in the progression of CRC.Material/MethodsGene and isoform expression datasets of CRC was downloaded from The Cancer Genome Atlas (TCGA). EBSeq of R was used for the normalization of gene and isoform expression, as well as the identification of differential expression genes (DEGs) and isoforms (DEIs) of CRC samples compared with normal samples. The enriched functions of DEGs and DEIs were obtained based on the Database for Annotation, Visualization and Integrated Discovery (DAVID). An independent dataset, GSE38832, was downloaded from the Gene Expression Omnibus (GEO) database for survival analysis of genes with sustained decreased/increased expression values at both gene and isoform levels with the development of CRC.ResultsA total of 2301 genes and 4241 isoforms were found to be significantly differentially expressed in stage I–IV CRC samples. They are closely associated with muscle or cell system activity. Sixteen genes were screened out with sustained decreased/increased expression values at both gene and isoform levels with the development of CRC. Aberrant CBX8 and CD96 expressions were found to be significantly associated with CRC survival.ConclusionsThrough combined analysis of gene and isoform expression profiles, we identified several potential biomarkers that may play an important role in the development of CRC and could be helpful in its early diagnosis and treatment.

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“…A clinical case report showed that CASZ1 gene expression was disrupted as a consequence of human papillomavirus DNA integration into the CASZ1 gene locus in a case of cervical cancer (10). In colorectal cancer, CASZ1 and MASP2 fusion transcript was detected, and this fusion product encodes a N-terminal truncated MASP2 that under the control of CASZ1 promoter (11). Our studies have shown that the CASZ1 gene is silenced in poor prognosis neuroblastoma (NB) patient tumor samples through loss of heterozygosity and/or EZH2-mediated epigenetic silencing (12).…”

Section: Introductionmentioning

confidence: 99%

Identification of CASZ1 NES reveals potential mechanisms for loss of CASZ1 tumor suppressor activity in neuroblastoma

et al. 2016

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As a transcription factor, localization to the nucleus and the recruitment of co-factors to regulate gene transcription is essential. Nuclear localization and nucleosome remodeling and histone deacetylase (NuRD) complex binding are required for the zinc finger transcription factor CASZ1 to function as neuroblastoma (NB) tumor suppressor. However, the critical amino acids (AAs) that are required for CASZ1 interaction with NuRD complex and the regulation of CASZ1 subcellular localization have not been characterized. Through alanine scanning, immunofluorescence cell staining and co-immunoprecipitation we define a critical region at the CASZ1 N-terminus (AA23-40) that mediates the CASZ1b nuclear localization and NuRD interaction. Furthermore, we identify a nuclear export signal (NES) at the N-terminus (AA176-192) that contributes to CASZ1 nuclear-cytoplasmic shuttling in a chromosomal maintenance 1 (CRM1)-dependent manner. An analysis of CASZ1 protein expression in a primary neuroblastoma tissue microarray shows that high nuclear CASZ1 staining is detected in tumors from NB patients with good prognoses. In contrast, cytoplasmic-restricted CASZ1 staining or low nuclear CASZ1 staining is found in tumors from patients with poor prognoses. These findings provide insight into mechanisms by which CASZ1 regulates transcription, and suggests that regulation of CASZ1 subcellular localization may impact its function in normal development and pathologic conditions such as neuroblastoma tumorigenesis.

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Novel RNA variants in colorectal cancers

Cited by 16 publications

References 55 publications

Downregulation of castor zinc finger 1 predicts poor prognosis and facilitates hepatocellular carcinoma progression via MAPK/ERK signaling

Downregulation of castor zinc finger 1 predicts poor prognosis and facilitates hepatocellular carcinoma progression via MAPK/ERK signaling

CBX8 and CD96 Are Important Prognostic Biomarkers of Colorectal Cancer

Identification of CASZ1 NES reveals potential mechanisms for loss of CASZ1 tumor suppressor activity in neuroblastoma

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