Loss of Linc01060 induces pancreatic cancer progression through vinculin-mediated focal adhesion turnover
Loss of Linc01060 induces pancreatic cancer progression through vinculin-mediated focal adhesion turnover
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Linc01060 的缺失通过纽蛋白介导的粘着斑更新诱导胰腺癌进展
DOI：
10.1016/j.canlet.2018.06.015
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发表时间：
2018-01-01
期刊：
影响因子：
9.7
通讯作者：
Qin, Renyi
中科院分区：
文献类型：
--
作者：
Shi, Xiuhui;Guo, Xingjun;Qin, Renyi
目前关于长链非编码rna （lncRNAs）参与癌症发展的知识有限。我们的目标是确定在胰腺癌进展中发挥重要作用的lncrna。我们筛选了胰腺癌组织中差异表达的lncrna。在349个差异表达的lncrna中，与正常胰腺组织相比，Linc01060在胰腺癌组织中的表达最低。胰腺癌组织中Linc01060低表达与预后不良显著相关。Linc01060在体外和体内均抑制胰腺癌的增殖和侵袭。Vinculin过表达抑制了linc0106010介导的FAK和paxillin磷酸化的增加，而Vinculin敲低逆转了linc01060介导的FAK抑制和局灶黏着转换的失活。Vinculin敲低也通过上调ERK活性加速胰腺癌细胞增殖。在生物学功能分析中，vinculin过表达消除了linc01060介导的胰腺癌细胞增殖和侵袭的抑制，而vinculin则抵消了linc01060介导的PC细胞增殖和侵袭的抑制。这些数据表明，Linc01060通过调节vinculin表达在抑制胰腺癌进展中起关键作用。这些发现提示Linc01060-vinculin-focal adhesion轴是胰腺癌治疗的一个治疗靶点。
There is currently limited knowledge regarding the involvement of long non-coding RNAs (lncRNAs) in cancer development. We aimed to identify lncRNAs with important roles in pancreatic cancer progression. We screened for lncRNAs that were differentially expressed in pancreatic cancer tissues. Among 349 differentially expressed lncRNAs, Linc01060 showed the lowest expression in pancreatic cancer tissues compared with normal pancreatic tissues. Lower Linc01060 expression in pancreatic cancer tissues was significantly associated with a poor prognosis. Linc01060 inhibited pancreatic cancer proliferation and invasion in vitro and in vivo. Vinculin over expression inhibited Linc0106010-mediated increases in FAK and paxillin phosphorylation, whereas vinculin knockdown reversed the Linc01060-mediated repression of FAK and inactivation of focal adhesion turnover. Vinculin knockdown also accelerated pancreatic cancer cell proliferation by upregulating ERK activity. In biological function analyses, vinculin overexpression abrogated Linc01060-mediated repression of pancreatic cancer cell proliferation and invasion, whereas vinculin counteracted the Linc01060-mediated repression of PC cell proliferation and invasion. These data demonstrate that Linc01060 plays a key role in suppressing pancreatic cancer progression by regulating vinculin expression. These findings suggest that the Linc01060-vinculin-focal adhesion axis is a therapeutic target for pancreatic cancer treatment.