MicroRNA 21 targets tumor suppressor genes in invasion and metastasis
MicroRNAs (miRNAs) are a class of naturally occurring small non coding RNAs that target protein coding mRNAs at the post transcriptional level. Our previous studies suggest that mir 21 functions as an oncogene and has a role in tumorigenesis, in part through regulation of the tumor suppressor gene tropomyosin 1 (TPM1) Given that TPM1 has been implicated in cell migration, in this study we further investigated the role of mir 21 in cell invasion and tumor metastasis. We found that suppression of mir 21 in metastatic breast cancer MDA MB 231 cells significantly reduced invasion and lung metastasis. Consistent with this, ectopic expression of TPM1 remarkably reduced cell invasion. Furthermore, we identified two additional direct mir 21 targets, programmed cell death 4 (PDCD4) and maspin, both of which have been implicated in invasion and metastasis. Like TPM1, PDCD4 and maspin also reduced invasiveness of MDA MB 231 cells. Finally, the expression of PDCD4 and maspin inversely correlated with mir 21 expression in human breast tumor specimens, indicating the potential regulation of PDCD4 and maspin by mir 21 in these tumors. Taken together, the results suggest that, as an oncogenic miRNA, mir 21 has a role not only in tumor growth but also in invasion and tumor metastasis by targeting multiple tumor/metastasis suppressor genes. Therefore, suppression of mir 21 may provide a novel approach for the treatment of advanced cancers.
Cell Research