Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 3132-3144 |
| Number of pages | 13 |
| Journal | Cancer Science |
| Volume | 110 |
| Issue number | 10 |
| DOIs | |
| Publication status | Published - Oct 1 2019 |
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All Science Journal Classification (ASJC) codes
- Oncology
- Cancer Research
Cite this
Oncogenic splicing abnormalities induced by DEAD-Box Helicase 56 amplification in colorectal cancer. / Kouyama, Yuta; Masuda, Takaaki; Fujii, Atsushi; Ogawa, Yushi; Sato, Kuniaki; Tobo, Taro; Wakiyama, Hiroaki; Yoshikawa, Yukihiro; Noda, Miwa; Tsuruda, Yusuke; Kuroda, Yousuke; Eguchi, Hidetoshi; Ishida, Fumio; Kudo, Shin ei; Mimori, Koshi.
In: Cancer Science, Vol. 110, No. 10, 01.10.2019, p. 3132-3144.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Oncogenic splicing abnormalities induced by DEAD-Box Helicase 56 amplification in colorectal cancer
AU - Kouyama, Yuta
AU - Masuda, Takaaki
AU - Fujii, Atsushi
AU - Ogawa, Yushi
AU - Sato, Kuniaki
AU - Tobo, Taro
AU - Wakiyama, Hiroaki
AU - Yoshikawa, Yukihiro
AU - Noda, Miwa
AU - Tsuruda, Yusuke
AU - Kuroda, Yousuke
AU - Eguchi, Hidetoshi
AU - Ishida, Fumio
AU - Kudo, Shin ei
AU - Mimori, Koshi
PY - 2019/10/1
Y1 - 2019/10/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85071359535&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85071359535&partnerID=8YFLogxK
U2 - 10.1111/cas.14163
DO - 10.1111/cas.14163
M3 - Article
C2 - 31390121
AN - SCOPUS:85071359535
VL - 110
SP - 3132
EP - 3144
JO - Cancer Science
JF - Cancer Science
SN - 1347-9032
IS - 10
ER -