Xie Mingxuan, Lu Xiaoxiao, Chen Qiong
Department of Geriatrics/Department of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, China.
National Clinical Research Centre for Geriatric Disorders, Department of Geriatrics, Xiangya Hospital, Central South University, Changsha, Hunan, China.
J Gene Med. 2020 Oct;22(10):e3215. doi: 10.1002/jgm.3215. Epub 2020 May 28.
The increasing incidence and unique biological features of lung cancer in women has prompted renewed interest in the role of sex hormones in this disease. We previously showed that progesterone (P4) inhibited lung cancer tumorigenesis and progression. Here, we investigated the effects of P4 on expression of long noncoding RNAs (lncRNAs) and target mRNAs in lung cancer cells.
We performed high-throughput microarray and bioinformatics analysis to identify differentially expressed lncRNAs and mRNAs in the untreated and the P4-treated A549 human lung cancer cells.
In total, 692 lncRNAs and 268 mRNAs were significantly differentially expressed in the P4-treated A549 cells compared to the untreated A549 cells (> 2-fold change, p < 0.05). Of the lncRNAs, 82 and 610 were up-regulated and down-regulated, respectively. Gene ontology, pathway and network analyses showed that many of the mRNAs were involved in the regulation of classical pathways, including Notch signaling. Differential expression of a lncRNA signature composed of NONHSAT000264, FR075921, FR324124, linc-TRIM58, RP1-93H18.7, RP11-120 K9.2, RP11-134F2.2 and NONHSAG024980 was validated by quantitatuve reverse transcriptase-polymerase chain reaction analysis.
This is the first report of differentially expressed lncRNAs in the P4-treated lung cancer cells. The results suggest that lncRNAs could serve as potential therapeutic targets for P4-sensitive lung cancer.
女性肺癌发病率的上升及其独特的生物学特征，促使人们重新关注性激素在该疾病中的作用。我们之前表明，孕酮（P4）可抑制肺癌的肿瘤发生和进展。在此，我们研究了P4对肺癌细胞中长链非编码RNA（lncRNA）和靶标mRNA表达的影响。
我们进行了高通量微阵列和生物信息学分析，以鉴定未处理和P4处理的A549人肺癌细胞中差异表达的lncRNA和mRNA。
与未处理的A549细胞相比，P4处理的A549细胞中共有692个lncRNA和268个mRNA显著差异表达（变化倍数>2倍，p<0.05）。在这些lncRNA中，分别有82个上调和610个下调。基因本体、通路和网络分析表明，许多mRNA参与经典通路的调控，包括Notch信号通路。由NONHSAT000264、FR075921、FR324124、linc-TRIM58、RP1-93H18.7、RP11-120K9.2、RP11-134F2.2和NONHSAG024980组成的lncRNA特征的差异表达通过定量逆转录-聚合酶链反应分析得到验证。
这是关于P4处理的肺癌细胞中lncRNA差异表达的首次报道。结果表明，lncRNA可能成为P4敏感型肺癌的潜在治疗靶点。
