MicroRNAs (miRNAs) have been proven to play crucial roles in cancer, including tumor chemotherapy resistance and metastasis of non-small-cell lung cancer (NSCLC). TGFβ signal pathway abnormality is widely found in cancer and correlates with tumor proliferation, apoptosis and metastasis. In a recent study published by researchers from Guangzhou Medical University, miR-17, 20a, 20b were detected down-regulated in A549/DDP cells (cisplatin resistance) compared with A549 cells (cisplatin sensitive) using LC Sciences miRNA microarray services. Over-expression of miR-17, 20a, 20b was shown to not only decrease cisplatin-resistant but also reduce migration by inhibiting epithelial-to-mesenchymal transition (EMT) in A549/DDP cells. These functions of miR-17, 20a, 20b are thought to be caused at least in part via inhibition of TGFβ signal pathway, as miR-17, 20a, 20b are shown to directly target and repress TGF-beta receptor 2 (TGFβR2) which is an important component of TGFβ signal pathway. Consequently, their study suggests that miRNA 17 family (including miR-17, 20a, 20b) can act as TGFβR2 suppressor for reversing cisplatin-resistant and suppressing metastasis in NSCLC.

(A) Clustering of cisplatin-resistant related miRNAs in A549 and A549/DDP cells. The vertical axis corresponds to the expression difference of miRNAs, A549 means A549 cells compared with A549/DDP cells in one microarray assay, A549/DDP means A549/DDP cells compared with A549 cells in another repeat microarray assay. The horizontal axis corresponds to miRNAs. miRNA expression levels were depicted as color variation from red (high expression) to green (low expression) according to color bar scale. (B) RT-PCR validated that miR-17, 20a, 20b expression levels were significantly lower in A549/DDP cells. (C) Over-expression or inhibition of miR-17, 20a, 20b significantly increased or decreased the growth-inhibitory effect of cisplatin in A549/DDP cells or A549 cells. *P<0.05. Results were representative of three experiments.

miR-17, 20a, 20b are low-expressed in A549/DDP cells and regulate cisplatin-resistant

journal.pone.0094639.g001


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Reference

Jiang Z, Yin J, Fu W, Mo Y, Pan Y. (2014) miRNA 17 Family Regulates Cisplatin-Resistant and Metastasis by Targeting TGFbetaR2 in NSCLC. PLoS ONE 9(4): e94639. [article]


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