miR-98 functions as a tumor suppressor in salivary adenoid cystic carcinomas

Abstract

Xiaonan Liu,1 Wenchao Zhang,1 Hua Guo,2 Jiuling Yue,1 Shanshan Zhuo1 1Department of Otorhinolaryngology and Maxillofacial Oncology, Tianjin Medical University Cancer Institute and Hospital, 2Laboratory of Cancer Cell Biology, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Cancer Institute, Tianjin Medical University Cancer Institute and Hospital, Tianjin, People’s Republic of China Purpose: miR-98, a member of the let-7 family of microRNAs, is downregulated in many malignant tumors and has been correlated with tumor progression. However, the roles of miR-98 in salivary adenoid cystic carcinomas (SACCs) are still unclear. Thus, we explored the role of miR-98 in the pathogenesis of SACCs. Methods: Reverse transcription-polymerase chain reaction was used to quantify miR-98 expression in SACC cell lines as well as in the primary tumors and adjacent tissues. Target gene prediction was carried out using softwares such as miRanda, PicTar, and TargetScan, and the neuroblastoma RAS viral oncogene homologue (N-RAS) was chosen as a potential target gene. Subsequently, the regulatory role of miR-98 on N-RAS expression was examined by Western blotting and immunofluorescence assays. N-RAS expression was detected in SACC tissues and SACC cell lines using immunohistochemistry and Western blot, respectively. Furthermore, the associations between N-RAS expression and clinicopathological features were analyzed. Finally, the effects of miR-98 on the proliferation and metastasis of SACC cell lines were determined. Results: miR-98 was downregulated in primary tissues and ACC-M cells. Meanwhile, N-RAS expression was significantly higher in SACC tissues than that in the adjacent tissues, and its overexpression was significantly associated with the clinical stage and tumor size. In addition, the overexpression of miR-98 in ACC-M cells inhibited cell proliferation, invasion, and migration in vitro. It also significantly decreased the expression of N-RAS and inhibited signaling through the PI3K/AKT and MAPK/ERK pathways. Conclusion: These results indicate that miR-98 possibly acts as a tumor suppressor in SACC by negatively regulating the oncogene N-RAS. Keywords: miR-98, salivary adenoid cystic carcinoma, metastasis, N-RAS

Keywords

• miR-98
• salivary adenoid cystic carcinoma
• metastasis
• N-RAS