PRKAR2A-derived circular RNAs promote the malignant transformation of colitis and distinguish patients with colitis-associated colorectal cancer.
PRKAR2A-derived circular RNAs promote the malignant transformation of colitis and distinguish patients with colitis-associated colorectal cancer.
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PRKAR2A 衍生的环状 RNA 促进结肠炎的恶性转化并区分结肠炎相关的结直肠癌患者
DOI：
10.1002/ctm2.683
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发表时间：
2022-03
影响因子：
10.6
通讯作者：
Zhi Q
中科院分区：
文献类型：
--
作者：
Wan D;Wang S;Xu Z;Zan X;Liu F;Han Y;Jiang M;Wu A;Zhi Q
近年来的研究表明，难治性炎症性肠病（IBD）引起的结肠炎症可引发结肠炎相关癌（CAC），但从炎症到癌的转变过程尚不清楚。本研究建立了小鼠结肠炎和CAC模型，并使用RNA-seq by circRNA微阵列鉴定不同比较（DSS vs. NC和AOM/DSS vs. DSS）中差异表达的circRNA和mRNA。通过生物信息学分析，寻找小鼠结肠炎和CAC的共同特征。K均值聚类算法将这些差异表达的circRNA打包到亚组分析中，数据强烈暗示mmu_circ_0001109与促炎信号密切相关，而mmu_circ_0001845与Wnt信号通路显著相关。我们随后的体内和体外数据证实，mmu_circ_0001109可通过上调Jak‐ STAT 3和NF‐kappa B信号通路加重结肠炎，mmu_circ_0001845通过Wnt信号通路促进CAC转化。通过小鼠和人之间的RNA爆破，鉴定了人RTEL 1-和PRKAR 2A-衍生的circRNA，其可能分别被认为是mmu_circ_0001109和mmu_circ_0001845的同源异型circRNA。临床数据显示，RTEL 1衍生的circRNA在人IBD和CAC中没有临床意义。然而，与mmu_circ_0001845具有高度RNA相似性的三种PRKAR 2A衍生的circRNA在CAC组织样品中显著上调，并促进了从结肠炎向CAC的转变。我们的研究结果表明，这些人PRKAR 2A衍生的circRNA可能是区分CAC患者和预测CAC预后的新候选者。
Emerging studies have proved that colonic inflammation caused by refractory inflammatory bowel disease (IBD) can initiate the colitis‐associated cancer (CAC), but the transition from inflammation to carcinoma is still largely unknown. In this study, mouse colitis and CAC models were established, and the RNA‐seq by circRNA microarray was employed to identify the differentially expressed circRNAs and mRNAs in different comparisons (DSS vs. NC and AOM/DSS vs. DSS). The bioinformatics analyses were used to search the common characteristics in mouse colitis and CAC. The K‐means clustering algorithm packaged these differential expressed circRNAs into subgroup analysis, and the data strongly implied that mmu_circ_0001109 closely correlated to the pro‐inflammatory signals, while mmu_circ_0001845 was significantly associated with the Wnt signalling pathway. Our subsequent data in vivo and in vitro confirmed that mmu_circ_0001109 could exacerbate the colitis by up‐regulating the Jak‐STAT3 and NF‐kappa B signalling pathways, and mmu_circ_0001845 promoted the CAC transformation through the Wnt signalling pathway. By RNA blasting between mice and humans, the human RTEL1‐ and PRKAR2A‐derived circRNAs, which might be considered as homeotic circRNAs of mmu_circ_0001109 and mmu_circ_0001845, respectively, were identified. The clinical data revealed that RTEL1‐derived circRNAs had no clinical significance in human IBD and CAC. However, three PRKAR2A‐derived circRNAs, which had the high RNA similarities to mmu_circ_0001845, were remarkably up‐regulated in CAC tissue samples and promoted the transition from colitis to CAC. Our results suggested that these human PRKAR2A‐derived circRNAs could be novel candidates for distinguishing CAC patients and predicted the prognosis of CAC.
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影响因子：
2.8
作者：
Ding S;Blue RE;Moorefield E;Yuan H;Lund PK
通讯作者：
Lund PK
影响因子：
--
作者：
Goi T;Kurebayashi H;Ueda Y;Naruse T;Nakazawa T;Koneri K;Hirono Y;Katayama K;Yamaguchi A
通讯作者：
Yamaguchi A
影响因子：
3.9
作者：
Ghasimi S;Wibom C;Dahlin AM;Brännström T;Golovleva I;Andersson U;Melin B
通讯作者：
Melin B
综合转录组分析鉴定出三阴性乳腺癌的新分子亚型和亚型特异性 RNA
DOI：
10.1186/s13058-016-0690-8
发表时间：
2016-03-15
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Liu YR;Jiang YZ;Xu XE;Yu KD;Jin X;Hu X;Zuo WJ;Hao S;Wu J;Liu GY;Di GH;Li DQ;He XH;Hu WG;Shao ZM
通讯作者：
Shao ZM
小鼠 CAC 模型中从结肠炎到 CRC 的基因表达变化的鉴定
影响因子：
3.7
作者：
Li X;Gao Y;Yang M;Zhao Q;Wang G;Yang YM;Yang Y;Liu H;Zhang Y
通讯作者：
Zhang Y