Deregulation of the MiR-193b-KRAS Axis Contributes to Impaired Cell Growth in Pancreatic Cancer.
Deregulation of the MiR-193b-KRAS Axis Contributes to Impaired Cell Growth in Pancreatic Cancer.
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DOI：
10.1371/journal.pone.0125515
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Chen J
中科院分区：
文献类型：
--
作者：
Jin X;Sun Y;Yang H;Li J;Yu S;Chang X;Lu Z;Chen J
通过上游信号调节 KRAS 活性揭示了一种有前景的胰腺癌治疗新方法；然而，microRNA相关的KRAS轴是否参与胰腺癌的癌变尚不清楚。在这里，我们将 miR-193b 鉴定为胰腺导管腺癌 (PDAC) 中的肿瘤抑制 miRNA。表达分析显示 miR-193b 在 (10/11) PDAC 样本和细胞系中下调。此外，我们发现 miR-193b 通过诱导 G1 期停滞并减少 S 期细胞比例，在 PDAC 细胞中发挥细胞周期制动器的作用，从而抑制细胞增殖。 miR-193b 还通过抑制贴壁依赖性生长来调节 PDAC 细胞的恶性转化表型。从机制上来说，KRAS 被证实是 miR-193b 的直接效应子，通过它调节 AKT 和 ERK 通路并抑制 PDAC 细胞的生长。综上所述，我们的研究结果表明 miR-193b 介导的 KRAS 轴失调与胰腺癌发生有关，并表明 miR-193b 可能是 PDAC 治疗的潜在有效靶点。
Modulation of KRAS activity by upstream signals has revealed a promising new approach for pancreatic cancer therapy; however, it is not clear whether microRNA-associated KRAS axis is involved in the carcinogenesis of pancreatic cancer. Here, we identified miR-193b as a tumor-suppressive miRNA in pancreatic ductal adenocarcinoma (PDAC). Expression analyses revealed that miR-193b was downregulated in (10/11) PDAC specimens and cell lines. Moreover, we found that miR-193b functioned as a cell-cycle brake in PDAC cells by inducing G1-phase arrest and reducing the fraction of cells in S phase, thereby leading to dampened cell proliferation. miR-193b also modulated the malignant transformation phenotype of PDAC cells by suppressing anchorage-independent growth. Mechanistically, KRAS was verified as a direct effector of miR-193b, through which the AKT and ERK pathways were modulated and cell growth of PDAC cells was suppressed. Taken together, our findings indicate that miR-193b-mediated deregulation of the KRAS axis is involved in pancreatic carcinogenesis, and suggest that miR-193b could be a potentially effective target for PDAC therapy.
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影响因子：
64.8
作者：
Baek, Daehyun;Villen, Judit;Shin, Chanseok;Camargo, Fernando D.;Gygi, Steven P.;Bartel, David P.
通讯作者：
Bartel, David P.
影响因子：
28.2
作者：
Collisson EA;Trejo CL;Silva JM;Gu S;Korkola JE;Heiser LM;Charles RP;Rabinovich BA;Hann B;Dankort D;Spellman PT;Phillips WA;Gray JW;McMahon M
通讯作者：
McMahon M
影响因子：
8.8
作者：
Eser, S.;Schnieke, A.;Schneider, G.;Saur, D.
通讯作者：
Saur, D.
影响因子：
5.2
作者：
Ikeda, Yushi;Tanji, Etsuko;Furukawa, Toru
通讯作者：
Furukawa, Toru
影响因子：
15.9
作者：
Collins, Meredith A.;Bednar, Filip;di Magliano, Marina Pasca
通讯作者：
di Magliano, Marina Pasca