MicroRNA-1246 expression associated with CCNG2-mediated chemoresistance and stemness in pancreatic cancer.
MicroRNA-1246 expression associated with CCNG2-mediated chemoresistance and stemness in pancreatic cancer.
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微小RNA - 1246的表达与胰腺癌中CCNG2介导的化疗耐药性及干性相关。
DOI：
10.1038/bjc.2014.454
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发表时间：
2014-10-14
影响因子：
8.8
通讯作者：
Ishii, H.
中科院分区：
文献类型：
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作者：
Hasegawa, S.;Eguchi, H.;Nagano, H.;Konno, M.;Tomimaru, Y.;Wada, H.;Hama, N.;Kawamoto, K.;Kobayashi, S.;Nishida, N.;Koseki, J.;Nishimura, T.;Gotoh, N.;Ohno, S.;Yabuta, N.;Nojima, H.;Mori, M.;Doki, Y.;Ishii, H.
胰腺癌对化疗和肿瘤复发的耐受性高，预后差，这些特性与肿瘤干细胞(CSCs)有关。MicroRNA(MiRNA)调控与CSCs相关的多种肿瘤进展的分子机制。本研究旨在确定候选miRNA并分析其临床意义。我们建立了耐吉西他滨的Panc1细胞，并通过球体形成诱导了CSC样特性。通过微阵列分析筛选出候选miRNAs。通过体外细胞生长和体内致瘤性实验进行过表达和基因敲除实验。应用免疫组织化学方法对24例胰腺癌标本进行激光捕获显微切割后检测其表达情况。通过CCNG2改变miR-1246的表达改变胰腺癌细胞的体外药物敏感性。在体内，我们发现miR-1246可以增加肿瘤的起始潜能和诱导耐药性。MiR-1246的高表达与预后不良相关，而CCNG2的表达在这些患者中显著降低。MIR-1246的表达通过CCNG2与化疗耐药和CSC样特性相关，并可预测胰腺癌患者的不良预后。
Pancreatic cancer has a poor prognosis because of its high refractoriness to chemotherapy and tumour recurrence, and these properties have been attributed to cancer stem cells (CSCs). MicroRNA (miRNA) regulates various molecular mechanisms of cancer progression associated with CSCs. This study aimed to identify the candidate miRNA and to characterise the clinical significance. We established gemcitabine-resistant Panc1 cells, and induced CSC-like properties through sphere formation. Candidate miRNAs were selected through microarray analysis. The overexpression and knockdown experiments were performed by evaluating the in vitro cell growth and in vivo tumourigenicity. The expression was studied in 24 pancreatic cancer samples after laser captured microdissection and by immunohistochemical staining. The in vitro drug sensitivity of pancreatic cancer cells was altered according to the miR-1246 expression via CCNG2. In vivo, we found that miR-1246 could increase tumour-initiating potential and induced drug resistance. A high expression level of miR-1246 was correlated with a worse prognosis and CCNG2 expression was significantly lower in those patients. miR-1246 expression was associated with chemoresistance and CSC-like properties via CCNG2, and could predict worse prognosis in pancreatic cancer patients.
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影响因子：
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作者：
Cui, D. W.;Cheng, Y. J.;Sun, G. G.
通讯作者：
Sun, G. G.
影响因子：
11.2
作者：
Li, Chenwei;Heidt, David G.;Simeone, Diane M.
通讯作者：
Simeone, Diane M.
影响因子：
64.8
作者：
Montagner, Marco;Enzo, Elena;Piccolo, Stefano
通讯作者：
Piccolo, Stefano
影响因子：
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作者：
Hermann, Patrick C.;Huber, Stephan L.;Heeschen, Christopher
通讯作者：
Heeschen, Christopher
影响因子：
8.8
作者：
Takeshita, N.;Hoshino, I.;Mori, M.;Akutsu, Y.;Hanari, N.;Yoneyama, Y.;Ikeda, N.;Isozaki, Y.;Maruyama, T.;Akanuma, N.;Komatsu, A.;Jitsukawa, M.;Matsubara, H.
通讯作者：
Matsubara, H.