Knockdown of MMP12 inhibits the growth and invasion of lung adenocarcinoma cells

Abstract

Matrix metalloproteinase-12 (MMP12) is involved in many pathological processes including cancer. The expression and function of MMP12 in lung adenocarcinoma (LAC) remain unclear. The present study aimed to investigate the correlation of MMP12 expression with LAC patients and clarify its role in growth and invasion of LAC cells. The expression of MMP12 in human LAC was examined by immunohistochemical assay using a tissue microarray procedure. A loss-offunction experiment was used for observing the effects of lentiviral vector-mediated MMP12 shRNA (shMMP12) on cell growth and invasion in LAC cell lines (A549), indicated by MTT and Transwell assays. We found that the expression of MMP12 protein was significantly increased in LAC tissues compared with that in adjacent non-cancerous tissues (ANCT) (57.69% vs. 32.69%, P = 0.019), and was closely correlated with the pathological stage and lymph node metastasis of LAC patients (P = 0.01; P = 0.003). Knockdown of MMP12 inhibited proliferation and invasion of LAC cells followed by the downregulation of proliferating cell nuclear antigen (PCNA) and vascular endothelial growth factor (VEGF).In conclusion, our findings show that high expression of MMP12 is correlated with the pathological stage and tumor metastasis of LAC patients, and knockdown of MMP12 suppresses the development of LAC cells, suggesting that MMP12 may be a promising therapeutic target for the treatment of LAC.

The prognostic values of matrix metalloproteinases in ovarian cancer

“…Matrix metalloproteinase-12 is involved in many pathological processes including cancer and it plays an essential role in invasion and metastasis of tumour cells. [17][18][19] Increased expression of MMP12 was observed in certain types of cancer, such as gastric cancer, 17 lung adenocarcinoma, 18 nasopharyngeal carcinoma 19 and cutaneous melanoma. 20 Knockdown of MMP12 inhibited proliferation and invasion of lung adenocarcinoma as well as nasopharyngeal carcinoma.…”

A molecular and staging model predicts survival in patients with resected non-small cell lung cancer

“…NSCLC patients with positive expression of MMP12 had a higher Hazard Ratio value for DFS and OS (1.72 (95%CI,1.30–2.26);1.73(95%CI1.28–2.54)). Knockdown of MMP12 inhibited proliferation and invasion of lung adenocarcinoma cells followed by the down-regulation of proliferating cell nuclear antigen (PCNA) and vascular endothelial growth factor (VEGF) [ 25 ].These results demonstrated that MMP12 played an important role in tumor invasiveness and metastasis.…”

Role of miR-647 in human gastric cancer suppression

“…Additionally, MMP2 and MMP12 belong to the group of MMPs, which are known for their key role in tumor metastasis and invasiveness (30,31). Recent studies have shown that inhibition of MMP2 and MMP12 suppresses the invasion of gastric and lung cancers (32,33). …”