Sekimoto Noboru, Suzuki Ayako, Suzuki Yutaka, Sugano Sumio
Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo 108‑8639, Japan.
Division of Translational Research, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwa, Chiba 277‑8577, Japan.
Mol Med Rep. 2017 Feb;15(2):534-542. doi: 10.3892/mmr.2016.6053. Epub 2016 Dec 15.
Lung cancer is the most common cause of cancer‑associated mortality worldwide, and the number of cases is increasing annually. Several studies have shown that microRNAs (miRNAs) control proliferation, differentiation, and apoptosis in various cell types, and increasing evidence indicates the presence of aberrant miRNA expression profiles and unique miRNA signaling pathways in several types of cancer. The present study aimed to identify miRNAs, which correlated specifically with the progression of lung cancer through the analysis of 57,100 transcripts and 1,341 small RNA expression profiles in 26 lung adenocarcinoma cell lines using next‑generation sequencing. The most marked negative correlation was found between the expression of hsa‑miR‑26a‑1 and messenger RNA (mRNA), and a list of mRNAs, which exhibited negative correlation with hsa‑miR‑26a‑1 were investigated. The most marked negative correlation was observed between the expression levels of hsa‑miR‑26a‑1 and high mobility group A1 (HMGA1). Using a lung adenocarcinoma cell line, the present study analyzed the effect of the overexpression of miR‑26a on the expression of HMGA1 and found that miR‑26a repressed the expression of HMGA1 by reducing the mRNA levels of HMGA1. Furthermore, it was demonstrated that the overexpression of miR‑26a in a lung adenocarcinoma cell line repressed cell migration, invasion and growth by targeting HMGA1. Taken together, the present study showed a significant negative correlation between the expression of miR‑26a and HMGA1 in 26 lung adenocarcinoma cell lines, and provided evidence that the suppression of miR‑26a supports the progression of cancer by stimulating the expression of HMGA1.
肺癌是全球癌症相关死亡的最常见原因,且病例数每年都在增加。多项研究表明,微小RNA(miRNA)可控制多种细胞类型的增殖、分化和凋亡,越来越多的证据表明,在几种类型的癌症中存在异常的miRNA表达谱和独特的miRNA信号通路。本研究旨在通过使用下一代测序分析26种肺腺癌细胞系中的57,100个转录本和1,341个小RNA表达谱,来鉴定与肺癌进展特异性相关的miRNA。在hsa-miR-26a-1的表达与信使核糖核酸(mRNA)之间发现了最显著的负相关,并对与hsa-miR-26a-1呈负相关的mRNA列表进行了研究。在hsa-miR-26a-1与高迁移率族蛋白A1(HMGA1)的表达水平之间观察到最显著的负相关。本研究使用一种肺腺癌细胞系,分析了miR-26a过表达对HMGA1表达的影响,发现miR-26a通过降低HMGA1的mRNA水平来抑制HMGA1的表达。此外,还证明了在肺腺癌细胞系中miR-26a的过表达通过靶向HMGA1来抑制细胞迁移、侵袭和生长。综上所述,本研究表明在26种肺腺癌细胞系中miR-26a与HMGA1的表达之间存在显著负相关,并提供了证据表明miR-26a的抑制通过刺激HMGA1的表达来支持癌症进展。