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The Epstein-Barr Virus-Encoded MicroRNA MiR-BART9 Promotes Tumor Metastasis by Targeting E-Cadherin in Nasopharyngeal Carcinoma

Figure 4

miR-BART9 enhances the metastatic activity of EBV-negative NPC cells in vivo.

(A) Primary tumor weights in nude mice subcutaneously injected with 1×106 BM1 cells expressing miR-BART9 or LacZ, at 8 weeks after inoculation. The data are presented as the means ± SEM (20 mice per group). (B) Hematoxylin/eosin (HE)-stained (left) and GFP-stained (right) sections of primary tumors isolated from mice that received BM1 cells expressing miR-BART9 or LacZ. Images were acquired at 100×. Scale bar = 500 µm. (C) Representative images of metastatic NPC cells in lymph nodes. HE-stained sections of lymph nodes isolated from mice that received BM1 cells expressing miR-BART9 or LacZ. Rectangular boxes indicate tumor cells in lymph nodes. Images were acquired at 100× and 200×. Scale bar = 200 µm. (D) Representative images of miR-BART9-expressing BM1 cells after metastasis to lung tissue. HE-stained and GFP-stained sections of lung tissues isolated from mice that received miR-BART9-expressing BM1 cells. Rectangular boxes indicate clusters of micrometastatic cells in the lung. Images were acquired at 100× and 400×. Scale bar = 500 µm and 100 µm. (E and F) Weights of primary tumors (E) and numbers of visible lung metastases (F) in nude mice that received 5×106 miR-BART9- or LacZ-expressing BM1 cells injected into the right flank, at week 8 after inoculation. The data are presented as the means ± SEM (each data point represents a different mouse; n = 5 mice per group). P value calculated by two-tailed Student's t-test. (G) Representative images of visible nodules on the surface of the lungs. Arrows indicate clusters of tumor cells that have colonized the lung tissue.

Figure 4

doi: https://doi.org/10.1371/journal.ppat.1003974.g004