Journal
CANCER BIOLOGY & THERAPY
Volume 13, Issue 5, Pages 330-340Publisher
TAYLOR & FRANCIS INC
DOI: 10.4161/cbt.19073
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Funding
- Natural Science Foundation of Jiangsu Province [BK2010578]
- National Natural Science Foundation of China [81101759]
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Purpose: To investigate the possible role of microRNAs in the resistance to platinum based chemotherapy in non-small cell lung cancer (NSCLC), explore their potential role and find potential biomarkers for prediction of the response to platinum. Results: 21 miRNAs were deregulated in A549/CDDP. Increased miR-21 expression significantly increased the resistance of A549 cell to platinum, whereas reduced miR-21 decreased the resistance of A549/CDDP cell. This finding was further validated in the tissue samples of 58 patients and it was found that miR-21 expression was significantly increased in platinum based chemotherapy-resistant patients (n = 58, p = 0.000). And increased miR-21 expression was associated with the shorter DFS (p = 0.008). Among these 58 patients, 32 had the corresponding plasma samples and similar tendencies were detected in 68.75% patients. Finally, transfection of A549/CDDP with anti-miR-21 increased the expression of PTEN and decreased Bcl-2. In contrast, pre-miR-21 decreased the expression of PTEN and increased Bcl-2 in A549. Patients and Methods: Microarray was employed to compare the expression of miRNAs between A549 and A549/CDDP cells. The effect of a differently expressed miRNA (miR-21) was examined on the sensitivity of cells to platinum. MiR21 expression in NSCLC tumor tissues and matched plasma sample was also analyzed by Real-time PCR. Conclusion: Our data suggests that the expression level of miR-21 in tumor tissue and plasma might be used as a biomarker to predict adjuvant platinum based chemotherapy response and disease free survival in patients with NSCLC. Thus, it may serve as a novel therapeutic target to modulate platinum-based chemotherapy.
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