The loss of miR-26a-mediated post-transcriptional regulation of cyclin E2 in pancreatic cancer cell proliferation and decreased patient survival.
The loss of miR-26a-mediated post-transcriptional regulation of cyclin E2 in pancreatic cancer cell proliferation and decreased patient survival.
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胰腺癌细胞增殖过程中 miR-26a 介导的细胞周期蛋白 E2 转录后调控的丧失和患者生存率下降
DOI：
10.1371/journal.pone.0076450
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Cai Z
中科院分区：
文献类型：
--
作者：
Deng J;He M;Chen L;Chen C;Zheng J;Cai Z
miR-26 a在肿瘤发生中起着关键作用，根据不同的肿瘤类型，它可以作为肿瘤抑制因子，也可以作为致癌miRNA。然而，miR-26 a在胰腺癌中的功能尚未明确阐明。本研究旨在确定miR-26 a在胰腺癌中的作用及其与胰腺癌患者生存率的关系。采用qRT-PCR方法检测15对胰腺导管腺癌（PDAC）及其癌旁良性胰腺组织（ABPT）中miR-26 a的表达。结果通过使用两组106个PDAC及其ABPT微阵列的原位杂交证实。确定miR-26 a表达与总生存期的相关性。分别使用Cell Counting Kit-8测定和流式细胞术评估用miR-26 a模拟物或miR-26 a抑制剂转染的Capan-2、SW-1990和Panc-1细胞的增殖和细胞周期分布。通过小鼠异种移植实验评价细胞致瘤性。Western blot和免疫组化检测细胞周期蛋白D2、E2、EZH 2和PCNA的表达。miR-26 a在胰腺导管上皮细胞胞浆中表达，而在PDAC组织中的表达与ABPT相比显著下调。miR-26 a低表达患者的生存期明显短于miR-26 a高表达患者。体外和体内试验表明，miR-26 a过表达导致细胞周期停滞，抑制细胞增殖，并降低肿瘤生长，这与cyclin E2下调有关。miR-26 a是胰腺导管癌的重要抑制因子，有望成为胰腺癌治疗的新靶点和预后因子。
miR-26a plays a critical role in tumorigenesis, either as a tumor suppressor or as an oncogenic miRNA, depending on different tumor types. However, the function of miR-26a in pancreatic cancer has not been clearly elucidated. The present study was designed to determine the roles of miR-26a in pancreatic cancer and its association with the survival of patients with pancreatic cancer. The expression of miR-26a was examined in 15 pairs of pancreatic duct adenocarcinoma (PDAC) and their adjacent benign pancreatic tissues (ABPT), by qRT-PCR. The results were confirmed by in situ hybridization using two panels of 106 PDACs and their ABPT microarray. The association of miR-26a expression with overall survival was determined. The proliferation and cell cycle distribution of Capan-2, SW-1990, and Panc-1 cells, transfected with miR-26a mimics or a miR-26a inhibitor, were assessed using the Cell Counting Kit-8 assay and flow cytometry, respectively. The cell tumorigenicity was evaluated via murine xenograft experiments. Cyclin D2, E2, EZH2, and PCNA levels were analyzed by Western blot and immunohistochemistry. miR-26a was expressed in the cytoplasm of pancreatic ductal epithelial cells, whereas its expression was significantly downregulated in PDAC tissues compared with that of ABPT. Patients with low miR-26a expression had a significantly shorter survival than those with high miR-26a expression. The in vitro and in vivo assays showed that overexpression of miR-26a resulted in cell cycle arrest, inhibited cell proliferation, and decreased tumor growth, which was associated with cyclin E2 downregulation. miR-26a is an important suppressor of pancreatic ductal carcinoma, and can prove to be a novel prognostic factor and therapeutic target for pancreatic cancer treatment.
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影响因子：
4.8
作者：
Jorgensen, Stine;Baker, Adam;Nielsen, Boye Schnack
通讯作者：
Nielsen, Boye Schnack
影响因子：
254.7
作者：
Jemal, Ahmedin;Siegel, Rebecca;Thun, Michael J.
通讯作者：
Thun, Michael J.
胰腺癌中的microRNA：病理，诊断和治疗意义。
影响因子：
9.7
作者：
Rachagani, Satyanarayana;Kumar, Sushil;Batra, Surinder K.
通讯作者：
Batra, Surinder K.
DOI：
10.1056/nejmoa0901282
发表时间：
2009-10-08
期刊：
The New England journal of medicine
影响因子：
--
作者：
Ji J;Shi J;Budhu A;Yu Z;Forgues M;Roessler S;Ambs S;Chen Y;Meltzer PS;Croce CM;Qin LX;Man K;Lo CM;Lee J;Ng IO;Fan J;Tang ZY;Sun HC;Wang XW
通讯作者：
Wang XW
影响因子：
5.8
作者：
Hayat, Matthew J.;Howlader, Nadia;Edwards, Brenda K.
通讯作者：
Edwards, Brenda K.