Abstract
miR-362 is a recently discovered member of the microRNA family, and it modulates a variety of physical activities and plays an important role in the occurrence and development of many tumors. However, the biological functions of hsa-miR-362-5p in non-small-cell lung carcinoma (NSCLC) are unknown. Transwell assay and colony formation were used to determine the migration, invasion, and proliferation of NSCLC cells in vitro. A subcutaneous tumor model in nude mice was established to detect NSCLC tumor growth in vivo. The direct binding of miR-362 to the 3′UTR of Semaphorin 3A (Sema3A) was confirmed by luciferase reporter assay. In this study, we found that the level of miR-362 was higher in NSCLC tissues than in adjacent normal tissues and that the level of miR-362 expression was also elevated in five NSCLC cell lines (A549, 95-D, H1299, H292, and H460) relative to a human normal lung epithelial cell line (BEAS2B). Furthermore, miR-362 promoted NSCLC cell invasion, migration, and colony formation in vitro and tumor formation in vivo. Next, we identified the miR-362 target gene Sema3A, which is significantly correlated with metastasis. Sema3A expression was increased in normal tissues relative to NSCLC tissues. This result is consistent with the fact that miR-362 expression is negatively correlated with Sema3A expression in clinical tissue samples and indicated that miR-362 can regulate Sema3A expression in NSCLC cells and consequently affect NSCLC invasion, migration, and colony formation. Taken together, these findings on the newly identified miR-362/Sema3A axis elucidate the molecular mechanism of NSCLC invasion and migration and could lead to a potential therapeutic target in NSCLC treatment.
Highlights
Lung cancer is the most frequently diagnosed cancer worldwide and the leading cause of cancer-related death [1]
A549 and 95-D by CRISPR/Cas9 technology to better understand the biological functions of miR-362 in the development of Non-small-cell lung cancer (NSCLC) [32,33,34,35,36]. In both A549 and 95-D cell lines, we found that knockout miR-362 significantly decreased cell invasion, migration, and colony formation ability (invasion ability, A549 in Figures 2(a) and 2(b), 95-D in Figures 2(c) and 2(d); migration ability, A549 in Figures 2(a) and 2(b), 95-D in 2(c) and 2(d); colony formation ability, A549 in Supplementary Figure 1(A, E), 95-D in Supplementary Figure 1(C, G)), whereas the cell cycle of the knockout group was not affected relative to the control group (Supplementary Figure 1(K, L))
We found that the level of miR-362 was significantly higher in NSCLC tissue than in matched normal tissue (Figures 1(a) and 1(b)) and that Semaphorin 3A (Sema3A) was directly regulated by miR-362
Summary
Lung cancer is the most frequently diagnosed cancer worldwide and the leading cause of cancer-related death [1]. Non-small-cell lung cancer (NSCLC) accounts for approximately 85% of lung cancer cases. Its one-year survival rate is less than 10%, and only 17.8% of patients survive for 5 years or more after lung cancer diagnosis [2, 3]. Approximately 40% of phase I and 60% of phase II patients with NSCLC die of distant metastasis in 5 years [4, 5]. No early symptoms have been observed before metastasis.
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