406941

MIR149

microRNA 149;MIR149;microRNA 149

hsa-mir-149

2q37.3

ncRNA

Deregulated molecular signaling pathways are responsible for the altered adhesive, migratory, and invasive properties of cancer cells. The different breast cancer subtypes are characterized by the expression of distinct miRNAs, short non-coding RNAs that posttranscriptionally modulate the expression of entire gene networks. Profiling studies have revealed downregulation of miR149 in basal breast cancer. Here, we show that miR149 expression severely impairs cell spreading, migration, and invasion of basal-like breast cancer cells. We identify signaling molecules, including the small GTPases Rap1a and Rap1b, downstream of integrin receptors as miR149 targets, providing an explanation for the defective Src and Rac activation during cell adhesion and spreading upon miR149 expression. Suppression of cell spreading by miR149 could be rescued, at least in part, by expression of constitutively active Rac. Finally, we demonstrate that increased miR149 levels block lung colonization in vivo. On the basis of our findings, we propose that miR149 downregulation in basal breast cancer facilitates the metastatic dissemination of tumor cells by supporting aberrant Rac activation. cancer Res; 74(18); 5256-65. (c)2014 AACR.

OBJECTIVE: To investigate the function and mechanism of miR-149 in nasopharyngeal carcinoma (NPC). METHODS: The expression of miR-149 was examined by real-time PCR and calculated by 2(-triangle uptriangle upCt) method. The cell proliferation was analyzed by MTT assay. The cell migration and invasion were shown by the wound healing assay and transwell migration assay, and the expression of E-cadherin was detected by Western blot. RESULTS: The expression of miR-149 was higher in NPC cell lines 5-8F and 6-10B than that in normal immortalized nasopharyngeal epithelial NP69. MTT assay showed that miR-149 promoted the proliferation of NPC cell lines. The wound healing assay showed miR-149 promoted the mobility and invasion of NPC cell lines. Inhibition of miR-149 reduced the ability of NPC cell lines to proliferate and invade. miR-149 downregulated the expression of E-cadherin, whereas antagomir which mediated knockdown of miR-149 significantly upregulated the expression of E-cadherin. CONCLUSION: miR-149 might be involved in the invasion and metastasis of NPC through regulation of epithelial-mesenchymal transition (EMT).