Overexpression of LIMD2 promotes the progression of non-small cell lung cancer

Oncol Lett. 2019 Aug;18(2):2073-2081. doi: 10.3892/ol.2019.10473. Epub 2019 Jun 12.

Abstract

LIM domain containing 2 (LIMD2) is a small LIM-only protein that has been demonstrated to promote tumor progression; however, the expression and function of LIMD2 in non-small cell lung cancer (NSCLC) has not previously been reported. In the present study, reverse transcription-quantitative PCR and western blot analysis were conducted to examine the mRNA and protein expression levels of LIMD2. Cell Counting Kit-8, Transwell and wound-healing assays were performed in order to examine cell proliferation, invasion and migration, respectively. The data revealed that the LIMD2 expression levels were significantly increased in NSCLC tissues and cell lines, compared with adjacent non-tumor tissues and normal lung epithelial cells, respectively. In addition, the high expression of LIMD2 was significantly associated with lymph node metastasis, distant metastasis and advanced clinical stage in NSCLC. The patients with NSCLC with a high expression of LIMD2 exhibited shorter survival times than those with low LIMD2 expression. The knockdown of LIMD2 caused remarkable decreases in NSCLC cell proliferation, migration and invasion. Bioinformatics analysis and luciferase reporter gene assay data further confirmed that LIMD2 was a direct target gene of microRNA-124 (miR-124), a well-known tumor suppressor in NSCLC. The expression of LIMD2 was negatively regulated by miR-124 in NSCLC cells. In addition, miR-124 was downregulated in NSCLC tissues compared with adjacent non-tumor tissues, and an inverse correlation was observed between the expression of LIMD2 and miR-124 in NSCLC tissues. In conclusion, the present study demonstrates that LIMD2 serves an oncogenic role in NSCLC, suggesting that it may be used as a potential therapeutic target for the treatment of NSCLC.

Keywords: LIM domain containing 2; microRNA-124; non-small cell lung cancer; oncogene.