Circular RNA Signature Predicts Gemcitabine Resistance of Pancreatic Ductal Adenocarcinoma.
Circular RNA Signature Predicts Gemcitabine Resistance of Pancreatic Ductal Adenocarcinoma.
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环状RNA特征预测胰腺导管腺癌的吉西他滨耐药性
DOI：
10.3389/fphar.2018.00584
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发表时间：
2018
影响因子：
5.6
通讯作者：
Huang Q
中科院分区：
文献类型：
--
作者：
Shao F;Huang M;Meng F;Huang Q
吉西他滨耐药是目前晚期胰腺癌化疗的主要问题。这种耐药性被认为是由药物代谢改变或癌细胞凋亡减少引起的。然而，胰腺癌吉西他滨耐药的潜在机制仍不清楚。在本研究中，我们建立了吉西他滨耐药的PANC-1（PANC-1-GR）细胞系，并通过RNA测序比较了PANC-1细胞和PANC-1-GR细胞之间的环状RNA（circRNA）谱。使用散点图和聚类热图分析来证明差异表达的circRNA。进行基因本体和通路分析以系统地定位与从我们的数据中鉴定的那些差异表达的circRNA功能相关的基因。通过qRT-PCR进一步验证了在PANC-1-GR细胞中通过RNAseq拾取的差异表达的circRNA的表达，并且最终将两种circRNA鉴定为最不同的靶标。与此一致，通过分析来自胰腺导管腺癌（PDAC）患者的血浆样品，这两种circRNA在吉西他滨无响应患者中显示出比响应患者更显著的表达。此外，我们发现两种circRNA的沉默可以恢复PANC-1-GR细胞对吉西他滨治疗的敏感性，而它们的过表达可以增加正常PANC-1和MIA PACA-2细胞的耐药性，这表明它们可能作为吉西他滨耐药的药物靶标。此外，基于对这两种circRNA的靶microRNA的相关性分析，探讨了它们之间的相互作用网络。总之，我们成功地建立了新的PANC-1-GR细胞，系统地表征了circRNA和miRNA谱，并鉴定了两种circRNA作为吉西他滨无应答PDAC患者的新型生物标志物和潜在治疗靶点。
Gemcitabine resistance is currently the main problem of chemotherapy for advanced pancreatic cancer patients. The resistance is thought to be caused by altered drug metabolism or reduced apoptosis of cancer cells. However, the underlying mechanism of Gemcitabine resistance in pancreatic cancer remains unclear. In this study, we established Gemcitabine resistant PANC-1 (PANC-1-GR) cell lines and compared the circular RNAs (circRNAs) profiles between PANC-1 cells and PANC-1-GR cells by RNA sequencing. Differentially expressed circRNAs were demonstrated using scatter plot and cluster heatmap analysis. Gene ontology and pathway analysis were performed to systemically map the genes which are functionally associated to those differentially expressed circRNAs identified from our data. The expression of the differentially expressed circRNAs picked up by RNAseq in PANC-1-GR cells was further validated by qRT-PCR and two circRNAs were eventually identified as the most distinct targets. Consistently, by analyzing plasma samples form pancreatic ductal adenocarcinoma (PDAC) patients, the two circRNAs showed more significant expression in the Gemcitabine non-responsive patients than the responsive ones. In addition, we found that silencing of the two circRNAs could restore the sensitivity of PANC-1-GR cells to Gemcitabine treatment, while over-expression of them could increase the resistance of normal PANC-1 and MIA PACA-2 cells, suggesting that they might serve as drug targets for Gemcitabine resistance. Furthermore, the miRNA interaction networks were also explored based on the correlation analysis of the target microRNAs of these two circRNAs. In conclusion, we successfully established new PANC-1-GR cells, systemically characterized the circRNA and miRNA profiles, and identified two circRNAs as novel biomarkers and potential therapeutic targets for Gemcitabine non-responsive PDAC patients.
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影响因子：
4.1
作者：
Qu S;Zhong Y;Shang R;Zhang X;Song W;Kjems J;Li H
通讯作者：
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影响因子：
11.2
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DOI：
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发表时间：
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期刊：
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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影响因子：
12.4
作者：
Zhuang J;Shen L;Yang L;Huang X;Lu Q;Cui Y;Zheng X;Zhao X;Zhang D;Huang R;Guo H;Yan J
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