Role of miR-10b in breast cancer metastasis - PubMed (original) (raw)

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Role of miR-10b in breast cancer metastasis

Li Ma. Breast Cancer Res. 2010.

Abstract

Ninety percent of cancer-related mortality is caused by metastasis. Current cancer treatments can control many primary tumors but rarely stop the metastatic spread. Accumulating evidence demonstrates that miRNAs are involved in cancer initiation and progression. Furthermore, several miRNAs have been found to regulate metastasis. In particular, recent studies provide the first functional evidence that overexpression of a specific miRNA, miR-10b, can contribute to the development of metastasis, which can be exploited therapeutically in treating breast cancer metastasis in mice. Further in-depth analysis should provide more precise evaluation of the roles, mechanisms, and therapeutic utility of this miRNA in breast cancer.

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Figure 1

Figure 1

miR-10b-mediated pathways in regulating tumor progression and metastasis. Multiple cancer gene products - including breast cancer metastasis suppressor-1 (BRMS1), latent membrane protein-1 (LMP1), CD44 and c-Src - regulate Twist expression. Among its multiple downstream targets/effectors, elevated expression of the transcription factor Twist in breast cancer cells induces the transcription of miR-10b. This miRNA suppresses synthesis of the HOXD10 protein, a negative regulator of breast cancer progression, permitting expression of pro-metastatic gene products, RhoC, urokinase plasminogen activator receptor (uPAR), α3-integrin, and MT1-MMP. This in turn favors cancer cell migration, invasion, and metastasis. Expression of HOXD10 is also inhibited by a long noncoding, metastasis-promoting RNA named HOTAIR. In addition, miR-10b targets KLF4 in esophageal cancer cells, leading to increased migration and invasion. In neurofibromatosis type 1-associated tumor cells, miR-10b targets the neurofibromin tumor suppressor, leading to activated RAS signaling. Color code: green, oncogenic and/or pro-metastatic factors; red, tumor-suppressing and/or metastasis-suppressing factors.

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