lncRNA LINC01234的敲低通过海绵化miR-513a-5p抑制肝癌的肿瘤发生。
Knockdown of lncRNA LINC01234 Suppresses the Tumorigenesis of Liver Cancer via Sponging miR-513a-5p.
作者信息
Xu Wen, Li Kesang, Song Changfeng, Wang Xiaotong, Li Yueqi, Xu Baixue, Liang Xin, Deng Wanli, Wang Junqing, Liu Jianwen
机构信息
State Key Laboratory of Bioreactor Engineering and Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, China.
Department of Hematology and Oncology, Hwa Mei Hospital, Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences, Ningbo, China.
出版信息
Front Oncol. 2020 Oct 16;10:571565. doi: 10.3389/fonc.2020.571565. eCollection 2020.
BACKGROUND
Liver cancer is a frequent malignancy with poor prognosis and high mortality all over the world. It has been reported many lncRNAs could modulate the tumorigenesis of liver cancer. To identify novel potential targets for liver cancer, the differential expressed lncRNAs between liver cancer and adjacent normal tissues was analyzed with bioinformatics tool.
METHODS
The differential expressed lncRNAs between liver cancer and adjacent normal tissues were analyzed with bioinformatics tool. Cell viability and proliferation was tested by CCK8 and Ki67, respectively. Apoptosis of liver cancer cells was tested by flow cytometry. Gene and protein expressions in liver cancer cells were measured by qRT-PCR and western blot, respectively. model of liver cancer was established to detect the effect of LINC01234 on liver cancer .
RESULTS
LINC01234 was found to be negatively correlated with the survival rate of patients with liver cancer. Moreover, knockdown of LINC01234 significantly suppressed the proliferation and invasion of liver cancer cells via inducing the apoptosis. Meanwhile, miR-513a-5p was sponged by LINC01234, and USP4 was found to be a direct target of miR-513a-5p. In addition, LINC01234 knockdown inhibited the tumorigenesis of liver cancer via inactivating TGF-β signaling. Furthermore, silencing of LINC01234 notably inhibited the tumor growth of liver cancer .
CONCLUSION
Downregulation of LINC01234 could inhibit the tumorigenesis of liver cancer via mediation of miR-513a-5p/USP4/TGF-β axis. Thus, LINC01234 might serve as a new target for the treatment of liver cancer.
背景
肝癌是一种常见的恶性肿瘤，在全球范围内预后较差且死亡率高。已有报道称许多长链非编码RNA（lncRNA）可调节肝癌的肿瘤发生。为了鉴定肝癌新的潜在靶点，利用生物信息学工具分析了肝癌组织与癌旁正常组织之间差异表达的lncRNA。
方法
利用生物信息学工具分析肝癌组织与癌旁正常组织之间差异表达的lncRNA。分别通过CCK8和Ki67检测细胞活力和增殖情况。通过流式细胞术检测肝癌细胞的凋亡情况。分别采用qRT-PCR和蛋白质免疫印迹法检测肝癌细胞中的基因和蛋白表达。建立肝癌模型以检测LINC01234对肝癌的影响。
结果
发现LINC01234与肝癌患者的生存率呈负相关。此外，敲低LINC01234可通过诱导凋亡显著抑制肝癌细胞的增殖和侵袭。同时，LINC01234可吸附miR-513a-5p，且发现USP4是miR-513a-5p的直接靶点。此外，敲低LINC01234可通过使TGF-β信号失活抑制肝癌的肿瘤发生。此外，沉默LINC01234可显著抑制肝癌的肿瘤生长。
结论
LINC01234的下调可通过miR-513a-5p/USP4/TGF-β轴的介导抑制肝癌的肿瘤发生。因此，LINC01234可能成为肝癌治疗的新靶点。
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