Zhang Feifei, Qin Shana, Xiao Xiang, Tan Yuefa, Hao Peng, Xu Yikai
Department of Imaging Diagnostic Center, Nanfang Hospital of Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.
PET/CT Center, Inner Mongolia People's Hospital, Hohhot, Inner Mongolia 010017, P.R. China.
Oncol Lett. 2019 Aug;18(2):2073-2081. doi: 10.3892/ol.2019.10473. Epub 2019 Jun 12.
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.
含LIM结构域蛋白2(LIMD2)是一种仅含LIM结构域的小蛋白,已被证明可促进肿瘤进展;然而,此前尚未报道过LIMD2在非小细胞肺癌(NSCLC)中的表达及功能。在本研究中,进行了逆转录定量PCR和蛋白质印迹分析,以检测LIMD2的mRNA和蛋白质表达水平。分别进行细胞计数试剂盒-8、Transwell和伤口愈合试验,以检测细胞增殖、侵袭和迁移情况。数据显示,与相邻非肿瘤组织和正常肺上皮细胞相比,NSCLC组织和细胞系中LIMD2的表达水平显著升高。此外,LIMD2的高表达与NSCLC中的淋巴结转移、远处转移及临床晚期显著相关。LIMD2高表达的NSCLC患者的生存时间比LIMD2低表达的患者短。敲低LIMD2导致NSCLC细胞增殖、迁移和侵袭显著降低。生物信息学分析和荧光素酶报告基因检测数据进一步证实,LIMD2是微小RNA-124(miR-124)的直接靶基因,miR-124是NSCLC中一种著名的肿瘤抑制因子。在NSCLC细胞中,LIMD2的表达受到miR-124的负调控。此外,与相邻非肿瘤组织相比,NSCLC组织中miR-124表达下调,且在NSCLC组织中观察到LIMD2与miR-124的表达呈负相关。总之,本研究表明LIMD2在NSCLC中起致癌作用,提示其可能作为NSCLC治疗的潜在靶点。