MiR-99a suppresses cell invasion and metastasis in nasopharyngeal carcinoma through targeting HOXA1.

BACKGROUND:Recent studies reported that miRNAs play important roles in the carcinogenesis and progression of nasopharyngeal carcinoma (NPC). Therefore, further studies are warranted to better elucidate the function and mechanism of miRNAs in NPC. METHODS:Quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the miR-99a expression in NPC cell lines and tissue samples. Wound healing, transwell migration and invasion, and lung metastatic colonization assays were performed to determine NPC cell migratory, invasive and metastatic abilities of NPC cells. Luciferase reporter assays, quantitative RT-PCR and Western blotting were used to validate the target of miR-99a. RESULTS:We found that miR-99a was significantly downregulated in NPC cell lines and tissue samples. Ectopic overexpression of miR-99a significantly inhibited NPC cell migration and invasion in vitro, and suppressed lung macroscopic and microscopic metastatic colonization in vivo. Conversely, silencing of miR-99a significantly promoted the migratory and invasive abilities of NPC cells. Furthermore, HOXA1 was validated as a direct target of miR-99a, and ectopic expression of HOXA1 could rescue the suppressive effect of miR-99a overexpression on NPC cell migration and invasion. CONCLUSION:Together, these results indicated that miR-99a could inhibit NPC invasion and metastasis by targeting HOXA1, thus providing a novel potential target for miRNA-based treatment for NPC patients in the future.