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Background Apelin plays an important role in many types of tumors. We aimed to identify the effects of miR‐195 on inhibiting apelin and clarify the regulating mechanism of miR‐195‐apelin in lung adenocarcinoma cells. Methods We detected the expression levels of apelin and miR‐195 in lung adenocarcinoma tissues and lung cancer cell lines using Western blotting and quantitative reverse transcription PCR assay, respectively. Luciferase reporter assay was used to confirm the target gene of miR‐195. The effects of miR‐195 and apelin on the proliferation and cell cycle of lung adenocarcinoma cells were assessed by methyl thiazolyl tetrazolium and colony formation assays, and flow cytometry. Wound‐healing and transwell invasion experiments were employed to examine cellular migration and invasion. A tumor xenograft model was then used to investigate the role of miR‐195 on tumor growth in vivo. Results The expression level of apelin and miR‐195 showed an inverse correlation in lung adenocarcinoma tissues and cell lines. Luciferase reporter assay suggested that miR‐195 directly targets apelin messenger RNA. Overexpression of miR‐195 significantly inhibited the proliferation, migration, and invasion of lung adenocarcinoma cells in vitro and suppressed tumor growth in vivo. Further analysis revealed that apelin is one of the functional target genes of miR‐195, and the overexpression of apelin efficiently inhibits the promotion of cell proliferation and invasion mediated by miR‐195 mimics in lung adenocarcinoma cells. Conclusions Our data constitute evidence that miR‐195 inhibits lung adenocarcinoma cell proliferation and invasion though targeting apelin and provides novel insight into the mechanism underlying the development of lung adenocarcinoma.

ObjectiveQujing City, Yunnan Province, China, has a high incidence of lung cancer and related mortality. The etiology of NSCLC in Qujing area and distribution of associated molecular aberrations has not been fully elucidated. This study aimed to reveal the profile of driver gene mutations in patients with non-small-cell lung cancer (NSCLC) in Qujing and explore their relationships with clinicopathological characteristics.MethodsIn this study, the mutation profiles of NSCLC driver genes, including EGFR, ALK, ROS1, KRAS, BRAF, RET, MET, HER2, NRAS, and PIK3CA, were investigated in patients with NSCLC from Qujing and compared with those from other regions in Yunnan Province. The associations between molecular mutations and clinicopathological characteristics were further analyzed.ResultsA distinct profile of driver gene mutations was discovered in patients with NSCLC from Qujing. Interestingly, a higher proportion of EGFR compound mutations, including G719X + S768I (19.65% vs 3.38%, P < 0.0001) and G719X + L861Q (21.10% vs 2.82%, P < 0.0001), was observed in patients with NSCLC in Qujing compared with patients in non-Qujing area, besides significantly different distributions of EGFR (46.01% vs. 51.07%, P = 0.0125), ALK (3.17% vs. 6.97%, P = 0.0012), ROS1 (0.5% vs. 2.02%, P = 0.0113), and KRAS (23.02% vs. 7.85%, P < 0.0001). Further, EGFR compound mutations were more likely associated with the occupation of patients (living/working in rural areas, e.g., farmers). Moreover, KRAS G12C was the dominant subtype (51.11% vs 25.00%, P = 0.0275) among patients with NSCLC having KRAS mutations in Qujing.ConclusionsPatients with NSCLC in Qujing displayed a unique profile of driver gene mutations, especially a higher prevalence of EGFR compound mutations and dominant KRAS G12C subtype, in this study, indicating a peculiar etiology of NSCLC in Qujing. Therefore, a different paradigm of therapeutic strategy might need to be considered for patients with NSCLC in Qujing.