Objectives: In this study, we assessed the expression and functional mechanism of microRNA-1197 (miR-1197) in human non-small cell lung cancer (NSCLC). Methods: In both NSCLC cell lines and NSCLC human tumors, qRT-PCR was used to assess miR-1197 expression. Through lentiviral transduction, miR-1197 was downregulated in two NSCLC cell lines, H510A and A549 cells. The functional regulations of miR-1197 downregulation on cancer cellin vitro proliferation and migration, as well as in vivo development, were assessed by MTT, transwell and xenograft assays, respectively. The association of miR-1197 on its putative downstream target gene, Homeobox C11 (HOXC11), was assessed by dual-luciferase reporter assay and qRT-PCR, respectively. Finally, HOXC11 was further inhibited in miR-1197-downregulated H510A and A549 cells to assess its mechanistic correlation with miR-1197 in regulating NSCLC in vitro proliferation and migration. Results: MiR-1197 was discovered to be predominantly upregulated in both NSCLC cancer cell lines and human tumors. MiR-1197 inhibition was able to suppress NSCLCin vitro proliferation and migration, as well as in vivo xenograft development. Biochemical analysis revealed that HOXC11 inversely regulated with miR-1197 in NSCLC. In double infected H510A and A549 cells, whose HOXC11 expression was further inhibited after miR-1197 downregulation, in vitro proliferation and migration were significantly augmented. Conclusion: MiR-1197 was upregulated in NSCLC and its downregulation has tumor-suppressing effects in NSCLC, very likely through inverse regulation on downstream target gene of HOXC11.

Stepwise progression from adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) to lepidic predominant adenocarcinoma (LPA) was proposed by various scholars. Interstitial tumor-associated macrophages (TAMs) and various potential chemokines involved in the progression from AIS/MIA to LPA were hypothesized. In the present study, immunohistochemistry or immunofluorescent double staining was used to detect the expression of the TAMs marker cluster of differentiation (CD) 68, tumor-derived colony-stimulating factor (CSF)-1, interleukin (IL)-6, matrix metalloproteinase (MMP)-2, E-cadherin and Snail in lung adenocarcinoma specimens, including AIS/MIA, LPA and other types. It was observed that infiltrating TAMs were negatively associated with the prognosis of patients, and that the infiltration degree of interstitial TAMs was higher in LPA than that in AIS/MIA. In addition, E-cadherin, Snail and MMP-2 expression were significantly correlated with the infiltration degree of TAMs. Survival analysis revealed that co-expression of CD68, CSF-1 and IL-6 was an independent prognostic factor. Stratified analysis demonstrated that, in AIS/MIA patients, there was a statistically significant difference between the number of TAMs (TAMs ≤25 and TAMs >25) in the CD68+CSF-1+IL-6+ group compared with other groups (including CD68+CSF-1-IL-6-, CD68+CSF-1+IL-6-, CD68+CSF-1-IL-6+ and CD68- groups). By contrast, in patients with TAMs >25 and in patients with positive CD68, CSF-1 and IL-6 expression, the survival rates were not significantly different between AIS/MIA and LPA. These results suggested that co-expression of TAMs marker CD68, CSF-1 and IL-6 may be a valuable independent prognostic predictor in lung adenocarcinoma. TAMs may facilitate AIS/MIA progression to LPA, which may be closely associated with the induction of the epithelial-mesenchymal transition.