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MicroRNA-485-5p suppresses growth and metastasis in non-small cell lung cancer cells by targeting IGF2BP2

Huang, Ri-sheng, Zheng, Yuan-liang, Li, Chang, Ding, Cheng, Xu, Chun, Zhao, Jun
Life sciences 2018 v.199 pp. 104-111
cell cycle checkpoints, cell proliferation, in vivo studies, lung neoplasms, lungs, lymph nodes, metastasis, mice, neoplasm cells, patients, prognosis
miR-485-5p serves as a tumor suppressor in several types of cancers. However, its prognostic and biological significance in non-small cell lung cancer (NSCLC) have not been determined yet. In the present study, we checked the expression of miR-485-5p in 87 pairs of paraffin-embedded lung cancer and matched non-cancerous specimens. The associations of miR-485-5p expression with aggressive parameters and survival in NSCLC were investigated. In addition, the function of miR-485-5p in controlling tumor growth and metastasis was clarified. We found that miR-485-5p was significantly downregulated in NSCLC, relative to adjacent non-cancerous lung tissues. Low miR-485-5p expression was significantly associated with advanced TNM stage, lymph node metastasis, and reduced patient survival. Overexpression of miR-485-5p significantly suppressed the growth and invasion, while knockdown of miR-485-5p had an opposite effect. Moreover, miR-485-5p overexpression caused a G0/G1 cell-cycle arrest and impaired TGF-β-induced epithelial-mesenchymal transition. Mechanistically, IGF2BP2 was identified as a novel direct target of miR-485-5p. Depletion of IGF2BP2 significantly inhibited NSCLC cell proliferation and invasion. Enforced expression of IGF2BP2 reversed the tumor suppressive activity of miR-485-5p. In vivo studies further demonstrated that overexpression of miR-485-5p interfered with the growth and metastasis of A549 cells in mice and reduced the expression of IGF2BP2. In conclusion, low miR-485-5p expression predicts poor prognosis in NSCLC patients. The miR-485-5p/IGF2BP2 axis orchestrates the growth and metastasis of NSCLC and represents a potential therapeutic target for this disease.