Genome-wide profiling of long non-coding RNA expression patterns in anthracycline-resistant breast cancer cells
Genome-wide profiling of long non-coding RNA expression patterns in anthracycline-resistant breast cancer cells
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DOI：
10.3892/ijo.2016.3665
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发表时间：
2016-10-01
影响因子：
5.2
通讯作者：
Ma, Xin
中科院分区：
文献类型：
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作者：
He, Dong-Xu;Zhang, Guang-Yuan;Ma, Xin
长的非编码RNA(LncRNAs)与癌症的进展有关。在本研究中，我们分析了阿霉素耐药和敏感的乳腺癌细胞中的lncRNA谱，发现在阿霉素耐药细胞中存在一组调控异常的lncRNA。失控的lncRNAs的表达与失控的mRNAs相关，并且在与癌症进展和化疗耐药发展相关的GO和KEGG通路中丰富。在这些LncRNA-mRNA相互作用中，一些LncRNA可能顺式调节邻近的蛋白编码基因，并参与化疗耐药。然后我们验证了lncRNA NONHSAT028712调控附近的CDK2，并干扰了细胞周期和化疗耐药性。此外，我们还鉴定了另一组通过与不同转录因子相互作用来反式调节基因的lncRNAs。例如，NONHSAT057282和NONHSAG023333分别调节化疗耐药性，并很可能分别与转录因子Elf1和E2F1相互作用。总之，在本研究中，我们首次报道了在阿霉素耐药的乳腺癌细胞中的lncRNA表达模式，并提供了一组新的lncRNA靶点，它们在顺式和反式作用模式下都介导了化疗耐药的发展。
Long non-coding RNAs (lncRNAs) are involved in cancer progression. In the present study, we analyzed the lncRNA profiles in adriamycin-resistant and-sensitive breast cancer cells and found a group of dysregulated lncRNAs in the adriamycin-resistant cells. Expression of the dysregulated lncRNAs was correlated with dysregulated mRNAs, and these were enriched in GO and KEGG pathways associated with cancer progression and chemoresistance development. Among these lncRNA-mRNA interactions, some lncRNAs may cis-regulate neighboring protein-coding genes and be involved in chemoresistance. We then validated that the lncRNA NONHSAT028712 regulated nearby CDK2 and interfered with the cell cycle and chemoresistance. Furthermore, we identified another group of lncRNAs that trans-regulated genes by interacting with different transcription factors. For example, NONHSAT057282 and NONHSAG023333 modulated chemoresistance and most likely interacted with the transcription factors ELF1 and E2F1, respectively. In conclusion, in the present study, we report for the first time the lncRNA expression patterns in adriamycin-resistant breast cancer cells, and provide a group of novel lncRNA targets that mediate chemoresistance development in both cis- and trans-action modes.