A Newly Identified lncBCAS1-4_1 Associated With Vitamin D Signaling and EMT in Ovarian Cancer Cells.
A Newly Identified lncBCAS1-4_1 Associated With Vitamin D Signaling and EMT in Ovarian Cancer Cells.
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新发现的 lncBCAS1-4_1 与卵巢癌细胞中维生素 D 信号传导和 EMT 相关
DOI：
10.3389/fonc.2021.691500
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发表时间：
2021
影响因子：
4.7
通讯作者：
Li B
中科院分区：
文献类型：
--
作者：
Xue Y;Wang P;Jiang F;Yu J;Ding H;Zhang Z;Pei H;Li B
长链非编码RNA（lncRNAs）因其在许多生物过程以及包括癌症在内的人类疾病中具有重要作用而被迅速鉴定出来。1α,25 - 二羟基维生素D3[1α,25(OH)2D3]及其类似物被广泛用作预防和治疗抗癌药物。然而，1α,25(OH)2D3调控的lncRNAs在卵巢癌中的表达谱仍有待阐明。在本研究中，我们基于微阵列数据发现了606个lncRNAs和102个mRNAs存在差异表达（DE）。基因本体论（GO）和京都基因与基因组百科全书（KEGG）通路分析表明，差异表达基因主要富集在转化生长因子 - β（TGF - β）、丝裂原活化蛋白激酶（MAPK）、Ras、磷脂酰肌醇 - 3 - 激酶 - 蛋白激酶B（PI3K - Akt）和Hippo信号通路以及维生素D相关通路中。我们进一步评估了将维生素D信号与上皮 - 间质转化（EMT）相关联的潜在lncRNAs，并首次鉴定出lncBCAS1 - 4_1。此外，我们发现上调最显著的lncBCAS1 - 4_1与CYP24A1（1α,25(OH)2D3的代谢酶）有75%的相同转录本。最后，建立了lncBCAS1 - 4_1功能获得细胞模型，该模型表明lncBCAS1 - 4_1的敲低抑制了卵巢癌细胞的增殖和迁移。此外，lncBCAS1 - 4_1能够抵抗1α,25(OH)2D3的抗肿瘤作用，这与锌指E - 盒结合同源框蛋白1（ZEB1）的上调有关。这些数据为lncRNAs作为1α,25(OH)2D3抗肿瘤作用的靶点提供了新的证据。
Long noncoding RNAs (lncRNAs) were identified rapidly due to their important role in many biological processes and human diseases including cancer. 1α,25-dihydroxyvitamin D3 [1α,25(OH)2D3] and its analogues are widely applied as preventative and therapeutic anticancer agents. However, the expression profile of lncRNAs regulated by 1α,25(OH)2D3 in ovarian cancer remains to be clarified. In the present study, we found 606 lncRNAs and 102 mRNAs that showed differential expression (DE) based on microarray data. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that the DE genes were mainly enriched in TGF-β, MAPK, Ras, PI3K-Akt, and Hippo signaling pathways, as well as the vitamin D-related pathway. We further assessed the potential lncRNAs that linked vitamin D signaling with EMT, and lncBCAS1-4_1 was identified in the first time. Moreover, we found that the most upregulated lncBCAS1-4_1 showed 75% same transcripts with CYP24A1 (metabolic enzyme of 1α,25(OH)2D3). Finally, the lncBCAS1-4_1 gain-of-function cell model was established, which demonstrated that the knockdown of lncBCAS1-4_1 inhibited the proliferation and migration of ovarian cancer cells. Furthermore, lncBCAS1-4_1 could resist the antitumor effect of 1α,25(OH)2D3, which was associated with upregulated ZEB1. These data provide new evidences that lncRNAs served as a target for the antitumor effect of 1α,25(OH)2D3.
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影响因子：
14.9
作者：
Kuleshov MV;Jones MR;Rouillard AD;Fernandez NF;Duan Q;Wang Z;Koplev S;Jenkins SL;Jagodnik KM;Lachmann A;McDermott MG;Monteiro CD;Gundersen GW;Ma'ayan A
通讯作者：
Ma'ayan A
癌症中的长非编码 RNA：信号传导电路。
影响因子：
19
作者：
Lin C;Yang L
通讯作者：
Yang L
影响因子：
15.3
作者：
Hmama, Z;Nandan, D;Sly, L;Knutson, K L;Herrera-Velit, P;Reiner, N E
通讯作者：
Reiner, N E
影响因子：
2.7
作者：
Hu N;Zhang H
通讯作者：
Zhang H
卵巢癌中长非编码 RNA 表达谱的分析。
影响因子：
2.9
作者：
Shen L;Liu W;Cui J;Li J;Li C
通讯作者：
Li C