Abstract
MicroRNAs (miRNA) are approximately 22-nucleotide noncoding RNAs that negatively regulate protein-coding gene expression in a sequence-specific manner via translational inhibition or mRNA degradation. Our recent studies showed that miRNAs exhibit genomic alterations at a high frequency and their expression is remarkably deregulated in ovarian cancer, strongly suggesting that miRNAs are involved in the initiation and progression of this disease. In the present study, we performed miRNA microarray to identify the miRNAs associated with chemotherapy response in ovarian cancer and found that let-7i expression was significantly reduced in chemotherapy-resistant patients (n = 69, P = 0.003). This result was further validated by stem-loop real-time reverse transcription-PCR (n = 62, P = 0.015). Both loss-of-function (by synthetic let-7i inhibitor) and gain-of-function (by retroviral overexpression of let-7i) studies showed that reduced let-7i expression significantly increased the resistance of ovarian and breast cancer cells to the chemotherapy drug, cis-platinum. Finally, using miRNA microarray, we found that decreased let-7i expression was significantly associated with the shorter progression-free survival of patients with late-stage ovarian cancer (n = 72, P = 0.042). This finding was further validated in the same sample set by stem-loop real-time reverse transcription-PCR (n = 62, P = 0.001) and in an independent sample set by in situ hybridization (n = 53, P = 0.049). Taken together, our results strongly suggest that let-7i might be used as a therapeutic target to modulate platinum-based chemotherapy and as a biomarker to predict chemotherapy response and survival in patients with ovarian cancer.
| Original language | English |
|---|---|
| Pages (from-to) | 10307-10314 |
| Number of pages | 8 |
| Journal | Cancer Research |
| Volume | 68 |
| Issue number | 24 |
| DOIs | |
| State | Published - Dec 15 2008 |
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All Science Journal Classification (ASJC) codes
- Cancer Research
- Oncology
Cite this
MicroRNA microarray identifies Let-7i as a novel biomarker and therapeutic target in human epithelial ovarian cancer. / Yang, Nuo; Kaur, Sippy; Volinia, Stefano; Greshock, Joel; Lassus, Heini; Hasegawa, Kosei; Liang, Shun; Leminen, Arto; Deng, Shan; Smith, Lori; Johnstone, Cameron N.; Chen, Xian-Ming; Liu, Chang Gong; Huang, Qihong; Katsaros, Dionyssios; Calin, George Adrian; Weber, Barbara L.; Bützow, Ralf; Croce, Carlo M.; Coukos, George; Zhang, Lin.
In: Cancer Research, Vol. 68, No. 24, 15.12.2008, p. 10307-10314.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - MicroRNA microarray identifies Let-7i as a novel biomarker and therapeutic target in human epithelial ovarian cancer
AU - Yang, Nuo
AU - Kaur, Sippy
AU - Volinia, Stefano
AU - Greshock, Joel
AU - Lassus, Heini
AU - Hasegawa, Kosei
AU - Liang, Shun
AU - Leminen, Arto
AU - Deng, Shan
AU - Smith, Lori
AU - Johnstone, Cameron N.
AU - Chen, Xian-Ming
AU - Liu, Chang Gong
AU - Huang, Qihong
AU - Katsaros, Dionyssios
AU - Calin, George Adrian
AU - Weber, Barbara L.
AU - Bützow, Ralf
AU - Croce, Carlo M.
AU - Coukos, George
AU - Zhang, Lin
PY - 2008/12/15
Y1 - 2008/12/15
N2 - MicroRNAs (miRNA) are approximately 22-nucleotide noncoding RNAs that negatively regulate protein-coding gene expression in a sequence-specific manner via translational inhibition or mRNA degradation. Our recent studies showed that miRNAs exhibit genomic alterations at a high frequency and their expression is remarkably deregulated in ovarian cancer, strongly suggesting that miRNAs are involved in the initiation and progression of this disease. In the present study, we performed miRNA microarray to identify the miRNAs associated with chemotherapy response in ovarian cancer and found that let-7i expression was significantly reduced in chemotherapy-resistant patients (n = 69, P = 0.003). This result was further validated by stem-loop real-time reverse transcription-PCR (n = 62, P = 0.015). Both loss-of-function (by synthetic let-7i inhibitor) and gain-of-function (by retroviral overexpression of let-7i) studies showed that reduced let-7i expression significantly increased the resistance of ovarian and breast cancer cells to the chemotherapy drug, cis-platinum. Finally, using miRNA microarray, we found that decreased let-7i expression was significantly associated with the shorter progression-free survival of patients with late-stage ovarian cancer (n = 72, P = 0.042). This finding was further validated in the same sample set by stem-loop real-time reverse transcription-PCR (n = 62, P = 0.001) and in an independent sample set by in situ hybridization (n = 53, P = 0.049). Taken together, our results strongly suggest that let-7i might be used as a therapeutic target to modulate platinum-based chemotherapy and as a biomarker to predict chemotherapy response and survival in patients with ovarian cancer.
AB - MicroRNAs (miRNA) are approximately 22-nucleotide noncoding RNAs that negatively regulate protein-coding gene expression in a sequence-specific manner via translational inhibition or mRNA degradation. Our recent studies showed that miRNAs exhibit genomic alterations at a high frequency and their expression is remarkably deregulated in ovarian cancer, strongly suggesting that miRNAs are involved in the initiation and progression of this disease. In the present study, we performed miRNA microarray to identify the miRNAs associated with chemotherapy response in ovarian cancer and found that let-7i expression was significantly reduced in chemotherapy-resistant patients (n = 69, P = 0.003). This result was further validated by stem-loop real-time reverse transcription-PCR (n = 62, P = 0.015). Both loss-of-function (by synthetic let-7i inhibitor) and gain-of-function (by retroviral overexpression of let-7i) studies showed that reduced let-7i expression significantly increased the resistance of ovarian and breast cancer cells to the chemotherapy drug, cis-platinum. Finally, using miRNA microarray, we found that decreased let-7i expression was significantly associated with the shorter progression-free survival of patients with late-stage ovarian cancer (n = 72, P = 0.042). This finding was further validated in the same sample set by stem-loop real-time reverse transcription-PCR (n = 62, P = 0.001) and in an independent sample set by in situ hybridization (n = 53, P = 0.049). Taken together, our results strongly suggest that let-7i might be used as a therapeutic target to modulate platinum-based chemotherapy and as a biomarker to predict chemotherapy response and survival in patients with ovarian cancer.
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U2 - 10.1158/0008-5472.CAN-08-1954
DO - 10.1158/0008-5472.CAN-08-1954
M3 - Article
VL - 68
SP - 10307
EP - 10314
JO - Journal of Cancer Research
JF - Journal of Cancer Research
SN - 0008-5472
IS - 24
ER -