miR‑888 regulates cancer progression by targeting multiple targets in lung adenocarcinoma.

ONCOLOGY REPORTS(2019)

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摘要
Aberrantly expressed miRNAs play a crucial role in the progression of lung adenocarcinoma. However, to date, the role of miR-888 in lung adenocarcinoma progression is unclear. In the present study, the biological function of miR-888 and its underlying mechanism in lung adenocarcinoma progression were explored. RT-qPCR was performed to detect the expression of miR-888 in 38 matched lung adenocarcinoma samples respectively. Next, the effects of miR-888 on the proliferation, invasion and migration of lung adenocarcinoma A549 cells were evaluated by a series of gain- and loss-of-function assays. Our results revealed that miR-888 was significantly upregulated in lung adenocarcinoma tissues, and its expression was markedly associated with clinical staging in patients. Moreover, ectopic expression of miR-888 in vitro was revealed to function as a double-edged sword in the progression of lung adenocarcinoma A549 cells by targeting multiple targets. Overexpression of miR-888 promoted the invasion and migration of lung adenocarcinoma A549 cells by targeting E-cadherin and tissue inhibitor of metalloproteinase 2. In addition, ectopic expression of miR-888 inhibited the proliferation of lung adenocarcinoma A549 cells by targeting cell division cycle 7 (CDC7). In addition, the immunohistochemical results and The Cancer Genome Atlas (TCGA) database revealed that CDC7 was significantly upregulated in lung adenocarcinoma tissues, suggesting that miR-888 may function as an oncogene in the progression of lung adenocarcinoma patients, and the miR-888/CDC7 axis was not the dominant pathway for CDC7 regulation in patients with lung adenocarcinoma. In conclusion, our findings indicated that miR-888 may act as a potential new therapeutic target for patients with lung adenocarcinoma.
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关键词
miR-888,lung adenocarcinoma,proliferation,invasion and migration,CDC7,E-cadherin,TIMP2
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