Abstract
Purpose: Recent studies revealed that both disseminated tumor cells and noncancerous cells contributed to cancer progression cooperatively in the bone marrow. Here, RNA-seq analysis of bone marrow from gastric cancer patients was performed to identify prognostic markers for gastric cancer. Experimental Design: Bone marrow samples from eight gastric cancer patients (stages I and IV: n = 4 each) were used for RNA-seq analysis. Results were validated through quantitative real-time PCR (qRT-PCR) analysis of HIST1H3D expression in 175 bone marrow, 92 peripheral blood, and 115 primary tumor samples from gastric cancer patients. miR-760 expression was assayed using qRT-PCR in 105 bone marrow and 96 primary tumor samples. Luciferase reporter assays were performed to confirm whether histone mRNAs were direct targets of miR-760. miR-760 expression was also evaluated in noncancerous cells from gastric cancer patients. Results: RNA-seq analysis of bone marrow samples from gastric cancer patients revealed higher expression of multiple histone mRNAs in stage IV patients. HIST1H3D expression in the bone marrow, peripheral blood, and primary tumor of stage IV patients was higher than that in stage I patients (P=0.0284, 0.0243, and 0.0006, respectively). In contrast, miR-760 was downregulated in the bone marrow and primary tumor of stage IV patients compared with stage I patients (P = 0.0094 and 0.0018, respectively). Histone mRNAand miR-760 interacted directly. Furthermore, miR-760 was downregulated in noncancerous mucosa in stage IV gastric cancer patients. Conclusion: Histone mRNA was upregulated, whereas miR-760 was downregulated in the bone marrow and primary tumor of advanced gastric cancer patients, suggesting that the histone mRNA/miR-760 axis had a crucial role in the development of gastric cancer.
| Original language | English |
|---|---|
| Pages (from-to) | 6438-6449 |
| Number of pages | 12 |
| Journal | Clinical Cancer Research |
| Volume | 19 |
| Issue number | 23 |
| DOIs | |
| Publication status | Published - Dec 1 2013 |
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All Science Journal Classification (ASJC) codes
- Oncology
- Cancer Research
Cite this
Contrasting expression patterns of histone mRNA and microRNA 760 in patients with gastric cancer. / Iwaya, Takeshi; Fukagawa, Takeo; Suzuki, Yutaka; Takahashi, Yusuke; Sawada, Genta; Ishibashi, Masahisa; Kurashige, Junji; Sudo, Tomoya; Tanaka, Fumiaki; Shibata, Kohei; Endo, Fumitaka; Katagiri, Hirokatsu; Ishida, Kaoru; Kume, Kohei; Nishizuka, Satoshi; Iinuma, Hisae; Wakabayashi, Go; Mori, Masaki; Sasako, Mitsuru; Mimori, Koshi.
In: Clinical Cancer Research, Vol. 19, No. 23, 01.12.2013, p. 6438-6449.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Contrasting expression patterns of histone mRNA and microRNA 760 in patients with gastric cancer
AU - Iwaya, Takeshi
AU - Fukagawa, Takeo
AU - Suzuki, Yutaka
AU - Takahashi, Yusuke
AU - Sawada, Genta
AU - Ishibashi, Masahisa
AU - Kurashige, Junji
AU - Sudo, Tomoya
AU - Tanaka, Fumiaki
AU - Shibata, Kohei
AU - Endo, Fumitaka
AU - Katagiri, Hirokatsu
AU - Ishida, Kaoru
AU - Kume, Kohei
AU - Nishizuka, Satoshi
AU - Iinuma, Hisae
AU - Wakabayashi, Go
AU - Mori, Masaki
AU - Sasako, Mitsuru
AU - Mimori, Koshi
PY - 2013/12/1
Y1 - 2013/12/1
N2 - Purpose: Recent studies revealed that both disseminated tumor cells and noncancerous cells contributed to cancer progression cooperatively in the bone marrow. Here, RNA-seq analysis of bone marrow from gastric cancer patients was performed to identify prognostic markers for gastric cancer. Experimental Design: Bone marrow samples from eight gastric cancer patients (stages I and IV: n = 4 each) were used for RNA-seq analysis. Results were validated through quantitative real-time PCR (qRT-PCR) analysis of HIST1H3D expression in 175 bone marrow, 92 peripheral blood, and 115 primary tumor samples from gastric cancer patients. miR-760 expression was assayed using qRT-PCR in 105 bone marrow and 96 primary tumor samples. Luciferase reporter assays were performed to confirm whether histone mRNAs were direct targets of miR-760. miR-760 expression was also evaluated in noncancerous cells from gastric cancer patients. Results: RNA-seq analysis of bone marrow samples from gastric cancer patients revealed higher expression of multiple histone mRNAs in stage IV patients. HIST1H3D expression in the bone marrow, peripheral blood, and primary tumor of stage IV patients was higher than that in stage I patients (P=0.0284, 0.0243, and 0.0006, respectively). In contrast, miR-760 was downregulated in the bone marrow and primary tumor of stage IV patients compared with stage I patients (P = 0.0094 and 0.0018, respectively). Histone mRNAand miR-760 interacted directly. Furthermore, miR-760 was downregulated in noncancerous mucosa in stage IV gastric cancer patients. Conclusion: Histone mRNA was upregulated, whereas miR-760 was downregulated in the bone marrow and primary tumor of advanced gastric cancer patients, suggesting that the histone mRNA/miR-760 axis had a crucial role in the development of gastric cancer.
AB - Purpose: Recent studies revealed that both disseminated tumor cells and noncancerous cells contributed to cancer progression cooperatively in the bone marrow. Here, RNA-seq analysis of bone marrow from gastric cancer patients was performed to identify prognostic markers for gastric cancer. Experimental Design: Bone marrow samples from eight gastric cancer patients (stages I and IV: n = 4 each) were used for RNA-seq analysis. Results were validated through quantitative real-time PCR (qRT-PCR) analysis of HIST1H3D expression in 175 bone marrow, 92 peripheral blood, and 115 primary tumor samples from gastric cancer patients. miR-760 expression was assayed using qRT-PCR in 105 bone marrow and 96 primary tumor samples. Luciferase reporter assays were performed to confirm whether histone mRNAs were direct targets of miR-760. miR-760 expression was also evaluated in noncancerous cells from gastric cancer patients. Results: RNA-seq analysis of bone marrow samples from gastric cancer patients revealed higher expression of multiple histone mRNAs in stage IV patients. HIST1H3D expression in the bone marrow, peripheral blood, and primary tumor of stage IV patients was higher than that in stage I patients (P=0.0284, 0.0243, and 0.0006, respectively). In contrast, miR-760 was downregulated in the bone marrow and primary tumor of stage IV patients compared with stage I patients (P = 0.0094 and 0.0018, respectively). Histone mRNAand miR-760 interacted directly. Furthermore, miR-760 was downregulated in noncancerous mucosa in stage IV gastric cancer patients. Conclusion: Histone mRNA was upregulated, whereas miR-760 was downregulated in the bone marrow and primary tumor of advanced gastric cancer patients, suggesting that the histone mRNA/miR-760 axis had a crucial role in the development of gastric cancer.
UR - http://www.scopus.com/inward/record.url?scp=84890255361&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84890255361&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-12-3186
DO - 10.1158/1078-0432.CCR-12-3186
M3 - Article
C2 - 24097871
AN - SCOPUS:84890255361
VL - 19
SP - 6438
EP - 6449
JO - Clinical Cancer Research
JF - Clinical Cancer Research
SN - 1078-0432
IS - 23
ER -