Long non-coding RNA FEZF1-AS1 promotes the proliferation and metastasis of hepatocellular carcinoma via targeting miR-107/Wnt/β-catenin axis.
Long non-coding RNA FEZF1-AS1 promotes the proliferation and metastasis of hepatocellular carcinoma via targeting miR-107/Wnt/β-catenin axis.
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DOI：
10.18632/aging.202960
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发表时间：
2021-05-23
期刊：
影响因子：
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通讯作者：
Zhang ZY
中科院分区：
文献类型：
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作者：
Yao J;Yang Z;Yang J;Wang ZG;Zhang ZY
肝细胞癌（HCC）是一个全球性的公共卫生问题，其分子机制仍不完全清楚。本研究旨在探讨长链非编码RNA (lncRNA) FEZF1-AS1在HCC进展中的作用及机制。应用RNA测序和定量实时聚合酶链反应（qRT- PCR）技术鉴定HCC组织和邻近正常组织中不同表达的lncRNAs。CCK8法检测细胞增殖，流式细胞术检测细胞凋亡。创面愈合实验和transwell实验测定细胞迁移和侵袭。为了验证lncRNA FEZF1-AS1在体内的功能，我们建立了肿瘤负荷模型。结果显示，lncRNA FEZF1-AS1水平在HCC肿瘤标本中显著升高，过表达FEZF1-AS1可促进HCC细胞的增殖、迁移和侵袭。在机制上，过表达FEZF1-AS1可降低miR-107的表达，从而抑制Wnt/β-catenin信号通路的激活。β-catenin过表达可促进细胞增殖、迁移和侵袭，而FEZF1-AS1下调可抑制β-catenin过表达。总之，我们的研究证明FEZF1-AS1通过靶向miR-107激活Wnt/β-catenin信号通路促进HCC进展，为HCC治疗提供了新的靶点。
Hepatocellular carcinoma (HCC) is a public health problem around the world, with the molecular mechanisms being still incompletely clear. This study was carried out to explore the role and mechanism of long-noncoding RNA (lncRNA) FEZF1-AS1 in HCC progression. RNA sequencing and quantitative real time polymerase chain reaction (qRT- PCR) were applied to identify differently expressed lncRNAs in HCC tissues and adjacent normal tissues. CCK8 assay was adopted to test cell proliferation and flow cytometry was taken to detect cell apoptosis. Wound healing assay and transwell experiment were performed to determine cell migration and invasion. To validate the function of lncRNA FEZF1-AS1 in vivo, tumor-burdened models were established. The results showed that lncRNA FEZF1-AS1 level was prominently enhanced in HCC tumor specimens and overexpression of FEZF1-AS1 promoted the proliferation, migration and invasion of HCC cells. In mechanism, overexpression of FEZF1-AS1 reduced the expression of miR-107 which inhibited the activation of Wnt/β-catenin signaling. Overexpression of β-catenin promoted cell proliferation, migration and invasion which were inhibited by FEZF1-AS1 downregulation. In conclusion, our study demonstrated that FEZF1-AS1 promoted HCC progression through activating Wnt/β-catenin signaling by targeting miR-107, which provided a novel target for the therapy of HCC.