Piplartine 通过 ICAT 抑制 LINC01391 调节的 Wnt/β-连环蛋白通路失活，从而抑制肝癌的增殖和侵袭。
Piplartine suppresses proliferation and invasion of hepatocellular carcinoma by LINC01391-modulated Wnt/β-catenin pathway inactivation through ICAT.
机构信息
Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, The Fifth Affiliated Hospital of Wenzhou Medical University, Affiliated Lishui Hospital of Zhejiang University, The Central Hospital of Zhejiang Lishui, Lishui, 323000, China; Department of Radiology, The Fifth Affiliated Hospital of Wenzhou Medical University, Affiliated Lishui Hospital of Zhejiang University, The Central Hospital of Zhejiang Lishui, Lishui, 323000, China.
Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, The Fifth Affiliated Hospital of Wenzhou Medical University, Affiliated Lishui Hospital of Zhejiang University, The Central Hospital of Zhejiang Lishui, Lishui, 323000, China; Department of Radiology, The Fifth Affiliated Hospital of Wenzhou Medical University, Affiliated Lishui Hospital of Zhejiang University, The Central Hospital of Zhejiang Lishui, Lishui, 323000, China.
出版信息
Cancer Lett. 2019 Sep 28;460:119-127. doi: 10.1016/j.canlet.2019.06.008. Epub 2019 Jun 14.
Although piplartine is regarded as an anticancer agent, the relationship between long noncoding RNAs (lncRNAs), which are involved in various diseases (e.g., tumors) and piplartine in hepatocellular carcinoma (HCC) remains unclear. We identified LINC01391 using microarray analysis and validated its expression by qRT-PCR. Functional assays were applied to evaluate the biological effects of LINC01391 and inhibitory of β-catenin and T-cell factor (ICAT) on HepG2 and SMMC-7721 cells. The binding relationship between LINC01391 and ICAT was determined by RNA pull-down and RNA immunoprecipitation (RIP). Results showed that piplartine attenuated cell proliferation and invasion but promoted cell apoptosis. Upregulation of LINC01391 induced by piplartine inhibited HCC cell proliferation, invasion in vitro, and tumor growth in vivo. LINC01391 interacted with ICAT and promoted its inhibitory effect on the Wnt/β-catenin pathway, as enhanced interaction between β-catenin and ICAT, and dampened interaction of β-catenin and TCF/LEF were induced by overexpression of LINC01391. Knockdown of ICAT also promoted cell proliferation in vitro and tumor growth in vivo. Our study supported a role for piplartine and LINC01391 in HCC treatment. We found that LINC01391 inhibited the Wnt/β-catenin pathway and suppressed tumor growth via ICAT.
尽管胡椒乙胺被认为是一种抗癌药物，但涉及各种疾病（例如肿瘤）的长链非编码 RNA（lncRNA）与肝癌（HCC）中的胡椒乙胺之间的关系尚不清楚。我们通过微阵列分析鉴定了 LINC01391，并通过 qRT-PCR 验证了其表达。应用功能测定来评估 LINC01391 和 β-连环蛋白和 T 细胞因子（ICAT）抑制剂对 HepG2 和 SMMC-7721 细胞的生物学效应。通过 RNA 下拉和 RNA 免疫沉淀（RIP）确定 LINC01391 和 ICAT 之间的结合关系。结果表明，胡椒乙胺减弱了细胞增殖和侵袭，但促进了细胞凋亡。胡椒乙胺上调 LINC01391 抑制 HCC 细胞增殖、体外侵袭和体内肿瘤生长。LINC01391 与 ICAT 相互作用并促进其对 Wnt/β-连环蛋白途径的抑制作用，因为 LINC01391 的过表达增强了 β-连环蛋白和 ICAT 之间的相互作用，并且减弱了 β-连环蛋白和 TCF/LEF 之间的相互作用。ICAT 的敲低也促进了体外细胞增殖和体内肿瘤生长。我们的研究支持胡椒乙胺和 LINC01391 在 HCC 治疗中的作用。我们发现 LINC01391 通过 ICAT 抑制 Wnt/β-连环蛋白途径并抑制肿瘤生长。
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