Objective: MicroRNAs (miRNAs) are endogenous, non-coding small RNAs, which play an important part in regulating organismal and pathological processes. Previous studies have shown that miRNA-199 acts as a tumor suppressor gene. However, we aimed to explore the characteristics and function of miRNA-199 in lung cancer (LCa), so as to further study its relationship with clinicopathological parameters and prognosis.
Patients and methods: Quantitative Real-time polymerase chain reaction (qRT-PCR) was used to detect miRNA-199 expression in 75 pairs of LCa tissues and normal adjacent tissues. In addition, the relationship between miRNA-199 expression and pathological features along with the prognosis of LCa patients were investigated. Besides, the expression level of miRNA-199 in LCa cells was further validated by qRT-PCR. In addition, miRNA-199 overexpression expression model was constructed in LCa cell lines H1299 and SPCA1. Cell counting kit-8 (CCK-8), cell cloning experiments, transwell invasion and migration assays were performed to analyze the effect of miRNA-199 on the biological function of LCa cells. Finally, the potential mechanism was explored using Western blot.
Results: qRT-PCR results displayed that the expression level of miRNA-199 in LCa tissues was significantly lower than that of the normal tissues. Compared with patients with high miRNA-199 expression, patients with lowly-expressed miRNA-199 had higher rates of lymph node metastases and distant metastases, and their overall survival rates were lower. In addition, the proliferation, invasion and metastasis of the miRNA-199 overexpression group were significantly increased than that in the negative control group. Western Blot results showed that the expression of key proteins in the EMT pathway, such as N-cadherin, Vimentin, β-catenin and MMP9 significantly increased in miRNA-199 overexpression group. Moreover, we also found that miRNA-199 and RGS17 have mutual regulation, which inhibited the malignant progression of LCa.
Conclusions: miRNA-199 expression was down-regulated in LCa and was significantly associated with LCa stage, distant metastasis, and poor prognosis. Besides, miRNA-199 may inhibit the malignant progression of LCa by interacting with RGS17.