A Yin-Yang 1/miR-30a regulatory circuit modulates autophagy in pancreatic cancer cells.
A Yin-Yang 1/miR-30a regulatory circuit modulates autophagy in pancreatic cancer cells.
复制标题
阴阳1/miR-30a调节电路调节胰腺癌细胞的自噬
DOI：
10.1186/s12967-017-1308-3
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发表时间：
2017-10-19
影响因子：
7.4
通讯作者：
Miao Y
中科院分区：
文献类型：
--
作者：
Yang C;Zhang JJ;Peng YP;Zhu Y;Yin LD;Wei JS;Gao WT;Jiang KR;Miao Y
自噬是一种高度调节的生物学过程，介导细胞内成分的降解。它是肿瘤细胞代谢和稳态所必需的。阴阳1号（Yin-Yang 1，YY 1）在多种肿瘤中参与自噬。然而，它在胰腺癌（最致命的人类恶性肿瘤之一）自噬中的作用尚不清楚。在此，我们研究了YY 1在胰腺癌细胞自噬中的功能及其作用机制。使用透射电子显微镜、免疫荧光和Western印迹法评估经历自噬的细胞的活性。荧光素酶活性测定、实时定量聚合酶链反应（RT-qPCR）和染色质免疫沉淀（ChIP）也用于鉴定YY 1的推定下游靶标。YY 1被证实在胰腺癌细胞中调节自噬。发现它直接调节miR-30 a的表达，miR-30 a是一种已知的自噬相关基因的调节剂。此外，miR-30 a的过表达减弱了YY 1的促自噬作用。累积起来，我们的数据表明，miR-30 a在反馈回路中起作用，以调节YY 1的促自噬活性。因此，胰腺癌细胞中的自噬可能部分受到紧密协调的YY 1/miR-30 a调控回路的调控。这些发现为胰腺癌治疗的发展提供了一个潜在的药物靶点。
Autophagy is a highly regulated biological process that mediates the degradation of intracellular components. It is required for tumor cell metabolism and homeostasis. Yin-Yang 1 (YY1) has been reported to be involved in autophagy in several carcinomas. However, its role in autophagy in pancreatic cancer, one of the deadliest human malignancies, is unknown. Here, we investigated the function of YY1 in pancreatic cancer cells autophagy and its mechanisms of action. The activity of cells undergoing autophagy was assessed using transmission electron microscopy, immunofluorescence, and Western blotting. A luciferase activity assay, real-time quantitative polymerase chain reaction (RT-qPCR), and chromatin immunoprecipitation (ChIP) were also used to identify putative downstream targets of YY1. YY1 was confirmed to regulate autophagy in pancreatic cancer cells. It was found to directly regulate the expression of miR-30a, a known modulator of autophagy-associated genes. Furthermore, overexpression of miR-30a attenuated the pro-autophagic effects of YY1. Cumulatively, our data suggest that miR-30a acts in a feedback loop to modulate the pro-autophagic activities of YY1. Thus, autophagy in pancreatic cancer cells may be regulated, in part, by a tightly coordinated YY1/miR-30a regulatory circuit. These findings provide a potential druggable target for the development of treatments for pancreatic cancer.
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影响因子：
7.8
作者：
ASHFORD, T P;PORTER, K R
通讯作者：
PORTER, K R
影响因子：
50.3
作者：
Wang H;Garzon R;Sun H;Ladner KJ;Singh R;Dahlman J;Cheng A;Hall BM;Qualman SJ;Chandler DS;Croce CM;Guttridge DC
通讯作者：
Guttridge DC
Yin Yang-1通过MUC4/ErbB2/p38/MEF2C依赖性机制下调MMP10抑制胰腺导管腺癌的侵袭和转移
影响因子：
37.3
作者：
Zhang JJ;Zhu Y;Xie KL;Peng YP;Tao JQ;Tang J;Li Z;Xu ZK;Dai CC;Qian ZY;Jiang KR;Wu JL;Gao WT;Du Q;Miao Y
通讯作者：
Miao Y
影响因子：
56.9
作者：
Kim, Jongpil;Inoue, Keiichi;Abeliovich, Asa
通讯作者：
Abeliovich, Asa
影响因子：
28.2
作者：
Yang A;Rajeshkumar NV;Wang X;Yabuuchi S;Alexander BM;Chu GC;Von Hoff DD;Maitra A;Kimmelman AC
通讯作者：
Kimmelman AC