YI-MING XU, SHENG-GUANG DING, LIANG SHEN, HAI-TAO HUANG, CHONG-JUN ZOHNG
Department of Thoracic and Cardiovascular Surgery, The Second Affiliated Hospital of Nantong University, Nantong 226001, China
Lung carcinoma represents the most deadly type of cancer worldwide. Increasing evidence suggests that microRNAs, a novel class of non-coding RNAs that function as endogenous suppressors of gene expression, are deregulated in non-small cell lung cancer. Although microRNA-222 overexpression has been described in NSCLC, the role of miR-222 and its target genes in erlotinib resistant PC-9 (PC-9/ER) cells remain poorly elucidated. Here we established miR-222 overexpression and low expression models by tran- sfection with miR-222 mimic, inhibitor or their negative controls. Cell proliferation was assessed by Cell Counting Kit-8 (CCK-8) and EdU incorporation assay.
MiR-222 and its putative target gene p27 expression level were determined using qRT-PCR and/or Western blot. MiR-222 ove- rexpression induced an enhancement of PC-9/ER proliferation in vitro. P27 expression was negatively regulated by miR-222 overex- pression at post-transcriptional level in PC-9/ER cells. Transfection of small interfering RNA (siRNA) for p27 increased PC-9/ER cell proliferation rate, validating that p27 is a target gene of miR-222 during PC-9/ER cell proliferation. This study suggests that miR-222 may regulate the acquired resistance of PC-9/ER cells to erlotinib by down-regulating p27. Inhibition of miR-222 might be a novel therapeutic strategy for TKI-resistant NSCLC.
microRNA-222, chemosensitivity, erlotinib, Non small-cell lung cancer (NSCLC)