Received for publication, December 12, 2006, and in revised form, March 15, 2007 Published, JBC Papers in Press, March 15, 2007, DOI 10.1074/jbc.M611393200 | Shuomin Zhu, Min-Liang Si, Hailong Wu, and Yin-Yuan Mo
This study investigates the role of MicroRNA-21 (miR-21) in tumor growth and identifies tropomyosin 1 (TPM1) as a potential target. MiR-21 is overexpressed in various tumors and its suppression inhibits tumor cell growth both in vitro and in vivo. The researchers used two-dimensional differential gel electrophoresis to identify TPM1 as a candidate miR-21 target. They found a putative binding site for miR-21 in the 3′-untranslated region (3′-UTR) of TPM1 variants V1 and V5. Cloning and analysis of the 3′-UTR of TPM1 into a luciferase reporter showed that miR-21 down-regulates luciferase activity, while anti-miR-21 up-regulates it. Western blot analysis confirmed that miR-21 regulates TPM1 protein levels, but not mRNA levels, suggesting translational regulation. Overexpression of TPM1 in breast cancer MCF-7 cells suppressed anchorage-independent growth, indicating that down-regulation of TPM1 by miR-21 may explain the inhibitory effect of miR-21 on tumor growth. This study provides evidence that miR-21 functions as an oncogene and highlights the importance of TPM1 in tumor suppression.This study investigates the role of MicroRNA-21 (miR-21) in tumor growth and identifies tropomyosin 1 (TPM1) as a potential target. MiR-21 is overexpressed in various tumors and its suppression inhibits tumor cell growth both in vitro and in vivo. The researchers used two-dimensional differential gel electrophoresis to identify TPM1 as a candidate miR-21 target. They found a putative binding site for miR-21 in the 3′-untranslated region (3′-UTR) of TPM1 variants V1 and V5. Cloning and analysis of the 3′-UTR of TPM1 into a luciferase reporter showed that miR-21 down-regulates luciferase activity, while anti-miR-21 up-regulates it. Western blot analysis confirmed that miR-21 regulates TPM1 protein levels, but not mRNA levels, suggesting translational regulation. Overexpression of TPM1 in breast cancer MCF-7 cells suppressed anchorage-independent growth, indicating that down-regulation of TPM1 by miR-21 may explain the inhibitory effect of miR-21 on tumor growth. This study provides evidence that miR-21 functions as an oncogene and highlights the importance of TPM1 in tumor suppression.