Small cell lung cancer growth is inhibited by miR-342 through its effect of the target gene IA-2

Journal of Translational Medicine

Research

Tao Cai¹  Gilberto N. Carmona¹  Liron Abuhatzira¹  Abner L. Notkins¹  Huanyu Xu¹ 

[1] Experimental Medicine Section, Laboratory of Sensory Biology, National Institute of Dental and Craniofacial Research (NIDCR), National Institutes of Health (NIH), B30/Rm106, 20892, Bethesda, MD, USA;

关键词: Small cell lung cancers (SCLC);    Dense-core vesicle (DCV);    microRNA;    Autocrine;    Therapeutic approach;   

DOI  :  10.1186/s12967-016-1036-0

 received in 2016-07-25, accepted in 2016-09-16,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundSmall cell lung cancers (SCLC) are tumors of neuroendocrine origin. Previous in vitro studies from our laboratory showed that SCLC expresses high levels of the transmembrane dense core vesicle protein IA-2 (islet cell antigen-2) as compared to normal lung cells. IA-2, through its effect on dense core vesicles (DCVs), is known to be involved in the secretion of hormones and neurotransmitters. It is believed that the dysregulated release of the neurotransmitter Acetylcholine (ACh) by DCVs has an autocrine effect on SCLC cell growth. Recently, we found that IA-2 is a target of the microRNA miR-342 and that miR-342 mimics suppress the expression of IA-2. The present experiments were initiated to see whether IA-2 and/or miR-342 affect the growth of SCLC.MethodsSCLC cell growth was evaluated following the knockdown of endogenous IA-2 with RNAi or by overexpressing miR-342 with a mimic. The secretion and content of ACh in SCLC cells was analyzed using a human acetylcholine ELISA (enzyme-linked immunosorbent assay) kit.ResultsThe knockdown of endogenous IA-2 by RNAi reduced SCLC cell growth within 4 days by 40 % or more. Similar results were obtained when these cell lines were transfected with a miR-342 mimic. The knockdown of IA-2 by RNAi or miR-342 with a mimic also resulted in a significant decrease in the secretion of ACh, one of the autocrine hormones secreted by SCLC. Further studies revealed that the growth of SCLC cell lines that had been treated with the miR-342 mimic was restored to nearly normal levels by treatment with ACh.ConclusionOur studies show for the first time that both miR-342 and its target gene IA-2 are involved in the growth process of SCLC cells and act by their effect on autocrine secretion. These findings point to possible new therapeutic approaches for the treatment of autocrine-induced tumor proliferation.

【 授权许可】

CC BY   
© The Author(s) 2016