Xue Wenhua, Li Lifeng, Tian Xin, Fan Zhirui, Yue Ying, Zhang Chaoqi, Ding Xianfei, Song Xiaoqin, Ma Bingjun, Zhai Yunkai, Lu Jingli, Kan Quancheng, Zhao Jie
Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China.
Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China.
Oncotarget. 2017 Mar 22;8(38):62868-62879. doi: 10.18632/oncotarget.16444. eCollection 2017 Sep 8.
Lung cancer is one of the leading causes of cancer-related death. Resistance to chemotherapy and molecularly targeted therapies is a major problem that can contribute substantially to high mortality. The roles of long non-coding RNAs (lncRNAs) in drug resistance of lung cancer are insufficiently understood. Here, we identified a distinct drug resistance-related transcriptional signature and constructed a functional lncRNA-mRNA co-expression network. We found that 34 lncRNAs and 103 mRNAs have differential expression in drug resistance of lung cancer, in which 10 lncRNAs were down regulated and 24 up regulated; 49 mRNAs were down regulated and 54 up regulated. LncRNAs-mRNAs expression network analysis revealed a role for lncRNAs in modulating cancer-related pathways. We also found that two pair lncRNAs and their subnetworks were highly related to drug resistance. NR_028502.1/NR_028505.1 were found differentially co-expressed with nine mRNAs, and highly correlated with better clinical outcome. NR_030725.1/NR_030726.1 co-expressed with eleven mRNAs, and were associated with poor survival in patients with lung cancer. Our work comprehensively identified expression signature of resistance-associated lncRNAs and their inter-regulated mRNAs in lung cancer.
肺癌是癌症相关死亡的主要原因之一。对化疗和分子靶向治疗的耐药性是一个重大问题，会极大地导致高死亡率。人们对长链非编码RNA（lncRNA）在肺癌耐药性中的作用了解不足。在此，我们鉴定了一种独特的与耐药性相关的转录特征，并构建了一个功能性lncRNA-mRNA共表达网络。我们发现34种lncRNA和103种mRNA在肺癌耐药性中存在差异表达，其中10种lncRNA下调，24种上调；49种mRNA下调，54种上调。lncRNAs-mRNAs表达网络分析揭示了lncRNAs在调节癌症相关通路中的作用。我们还发现两对lncRNA及其子网与耐药性高度相关。发现NR_028502.1/NR_028505.1与9种mRNA差异共表达，且与更好的临床结果高度相关。NR_030725.1/NR_030726.1与11种mRNA共表达，并与肺癌患者的不良生存相关。我们的工作全面鉴定了肺癌中与耐药相关的lncRNA及其相互调节的mRNA的表达特征。
