Phosphoserine Phosphatase Is a Novel Prognostic Biomarker on Chromosome 7 in Colorectal Cancer

Sato, Kuniaki; Masuda, Takaaki; Hu, Qingjiang; Tobo, Taro; Kidogami, Shinya; Ogawa, Yushi; Saito, Tomoko; Nambara, Sho; Komatsu, Hisateru; Hirata, Hidenari; Sakimura, Shotaro; Uchi, Ryutaro; Hayashi, Naoki; Iguchi, Tomohiro; Eguchi, Hidetoshi; Ito, Shuhei; Nakagawa, Takashi; Mimori, Koshi

doi:10.21873/anticanres.11574

Cited by 34 publications

(29 citation statements)

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“…RNA was extracted from frozen tissue specimens and cell lines using ISOGEN-II (Nippon Gene), and RT-quantitative polymerase chain reaction (qPCR) was carried out as previously described. 11 Gene expression was quantified using the follow-…”

Section: Rna Extraction and Reverse Transcriptionquantitative Polymmentioning

confidence: 99%

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Oncogenic splicing abnormalities induced by DEAD‐Box Helicase 56 amplification in colorectal cancer

et al. 2019

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Alternative splicing, regulated by DEAD‐Box Helicase (DDX) families, plays an important role in cancer. However, the relationship between the DDX family and cancer has not been fully elucidated. In the present study, we identified a candidate oncogene DDX56 on Ch.7p by a bioinformatics approach using The Cancer Genome Atlas (TCGA) dataset of colorectal cancer (CRC). DDX56 expression was measured by RT‐qPCR and immunochemical staining in 108 CRC patients. Clinicopathological and survival analyses were carried out using three CRC datasets. Biological roles of DDX56 were explored by gene set enrichment analysis (GSEA), and cell proliferation in vitro and in vivo, cell cycle assays, and using DDX56‐knockdown or overexpressed CRC cells. RNA sequencing was carried out to elucidate the effect of DDX56 on mRNA splicing. We found that DDX56 expression was positively correlated with the amplification of DDX56 and was upregulated in CRC cells. High DDX56 expression was associated with lymphatic invasion and distant metastasis and was an independent poor prognostic factor. In vitro analysis, in vivo analysis and GSEA showed that DDX56 promoted proliferation ability through regulating the cell cycle. DDX56 knockdown reduced intron retention and tumor suppressor WEE1 expression, which functions as a G2‐M DNA damage checkpoint. We have identified DDX56 as a novel oncogene and prognostic biomarker of CRC that promotes alternative splicing of WEE1.

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Section: Rna Extraction and Reverse Transcriptionquantitative Polymmentioning

confidence: 99%

“…Using this screening approach, we previously identified phosphoserine phosphatase (PSPH), located on Ch.7p, as a driver gene in CRC. 11 Herein, we used our screening method and identified DEAD-Box helicase (DDX56), as a candidate oncogene. DDX56 is located on Ch.7p and is a member of the DDX family, known to regulate alternative splicing.…”

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Oncogenic splicing abnormalities induced by DEAD‐Box Helicase 56 amplification in colorectal cancer

et al. 2019

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“…We recently established a screening system using a bioinformatics approach with public datasets to identify candidate oncogenes in CRC. Using this system, we identified phosphoserine phosphatase ( PSPH ) and eIF5‐mimic protein 1 ( 5MP1 ) as potential oncogenes on Ch.7p in CRC . Furthermore, we found that their expression was significantly associated with cell cycle progression genes and was an independent poor prognostic factor in patients with CRC.…”

Section: Introductionmentioning

confidence: 99%

GTF2IRD1 on chromosome 7 is a novel oncogene regulating the tumor‐suppressor gene TGFβR2 in colorectal cancer

et al. 2019

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Chromosome 7q (Ch.7q) is clonally amplified in colorectal cancer (CRC). We aimed to identify oncogenes on Ch.7q that are overexpressed through DNA copy number amplification and determine the biological and clinical significance of these oncogenes in CRC. We identified general transcription factor 2I repeat domain-containing protein 1 (GTF2IRD1) as a potential oncogene using a CRC dataset from The Cancer Genome Atlas with a bioinformatics approach. We measured the expression of GTF2IRD1 in 98 patients with CRC using immunohistochemistry and RT-quantitative PCR (RT-qPCR). The biological effects of GTF2IRD1 expression were explored by gene set enrichment analysis (GSEA). Next, we undertook in vitro cell proliferation and cell cycle assays using siGTF2IRD1-transfected CRC cells. We further investigated the oncogenic mechanisms through which GTF2IRD1 promoted CRC progression. Finally, we assessed the clinical significance of GTF2IRD1 expression by RT-qPCR. GTF2IRD1 was overexpressed in tumor cells and liver metastatic lesions. The GSEA revealed a positive correlation between GTF2IRD1 expression and cell cycle progression-related genes. GTF2IRD1 knockdown inhibited cell proliferation and induced cell cycle arrest in Smad4-mutated CRC. GTF2IRD1 downregulated the expression of the gene encoding transforming growth factor β receptor 2 (TGFβR2), a tumor-suppressor gene in Smad4-mutated CRC. On multivariate analysis, high GTF2IRD1 expression was an independent poor prognostic factor. Clinicopathological analysis showed that GTF2IRD1 expression was positively correlated with liver metastasis. In conclusion, GTF2IRD1 promoted CRC progression by downregulating TGFβR2 and could be a prognostic biomarker on Ch.7q in CRC. GTF2IRD1 could also be a novel oncogene in CRC. K E Y W O R D Scell cycle, colorectal cancer, GTF2IRD1, oncogene, TGFβR2

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“…Prognostic factors are needed to identify patients at risk and to optimize treatment. Several factors have been suggested to have an impact on the outcome in terms of survival or locoregional recurrence such as DDR2 expression, phosphoserine phosphatase, preoperative total lesion glycolysis (TLG), nutritional status and lower body mass index (8)(9)(10)(11)(12)(13)(14). These factors can help to understand a patient's prognosis and optimize treatment allocation.…”

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A Scoring System to Predict the Development of Bone Metastasis After Radical Resection of Colorectal Cancer

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et al. 2017

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Phosphoserine Phosphatase Is a Novel Prognostic Biomarker on Chromosome 7 in Colorectal Cancer

Abstract: PSPH could be a novel prognostic biomarker with malignant potential on Ch.7p in CRC.

Cited by 34 publications

References 5 publications

Oncogenic splicing abnormalities induced by DEAD‐Box Helicase 56 amplification in colorectal cancer

Oncogenic splicing abnormalities induced by DEAD‐Box Helicase 56 amplification in colorectal cancer

GTF2IRD1 on chromosome 7 is a novel oncogene regulating the tumor‐suppressor gene TGFβR2 in colorectal cancer

A Scoring System to Predict the Development of Bone Metastasis After Radical Resection of Colorectal Cancer

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