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M6A-mediated upregulation of LINC00958 increases lipogenesis and acts as a nanotherapeutic target in hepatocellular carcinoma 期刊论文 WOS高被引论文

编号：

16F4977319C9DF9530934E7B93BE3D4F
作者：

Zuo, Xueliang(左学良)#^[1,2,3]Chen, Zhiqiang(陈志强)#^[2]Gao, Wen(高雯)#^[4]Zhang, Yao^[2];Wang, Jinguo(汪进国)^[1]Wang, Junfeng(王俊峰)^[1]Cao, Ming^[5];Cai, Juan(蔡娟)*^[3,6,7,8]Wu, Jindao(吴金道)*^[2,9]Wang, Xuehao(王学浩)*^[2]
语种：

英文
期刊：

JOURNAL OF HEMATOLOGY & ONCOLOGY ISSN：1756-8722 2020 年 13 卷 1 期 ; JAN 8
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关键词：

LINC00958 Hepatocellular carcinoma N-6-methyladenosine Lipogenesis HDGF
摘要：

Background Long non-coding RNAs (lncRNAs) possess significant regulatory functions in multiple biological and pathological processes, especially in cancer. Dysregulated lncRNAs in hepatocellular carcinoma (HCC) and their therapeutic applications remain unclear. Methods Differentially expressed lncRNA profile in HCC was constructed using TCGA data. LINC00958 expression level was examined in HCC cell lines and tissues. Univariate and multivariate analyses were performed to demonstrate the prognostic value of LINC00958. Loss-of-function and gain-of-function experiments were used to assess the effects of LINC00958 on cell proliferation, motility, and lipogenesis. Patient-derived xenograft model was established for in vivo experiments. RNA immunoprecipitation, dual luciferase reporter, biotin-labeled miRNA pull-down, fluorescence in situ hybridization, and RNA sequencing assays were performed to elucidate the underlying molecular mechanisms. We developed a PLGA-based nanoplatform encapsulating LINC00958 siRNA and evaluated its superiority for systemic administration. Results We identified a lipogenesis-related lncRNA, LINC00958, whose expression was upregulated in HCC cell lines and tissues. High LINC00958 level independently predicted poor overall survival. Functional assays showed that LINC00958 aggravated HCC malignant phenotypes in vitro and in vivo. Mechanistically, LINC00958 sponged miR-3619-5p to upregulate hepatoma-derived growth factor (HDGF) expression, thereby facilitating HCC lipogenesis and progression. METTL3-mediated N-6-methyladenosine modification led to LINC00958 upregulation through stabilizing its RNA transcript. A PLGA-based nanoplatform loaded with si-LINC00958 was developed for HCC systemic administration. This novel drug delivery system was controlled release, tumor targeting, safe, and presented satisfactory antitumor efficacy. Conclusions Our results delineate the clinical significance of LINC00958 in HCC and the regulatory mechanisms involved in HCC lipogenesis and progression, providing a novel prognostic indicator and promising nanotherapeutic target.
推荐引用方式
GB/T 7714：

Zuo Xueliang,Chen Zhiqiang,Gao Wen, et al. M6A-mediated upregulation of LINC00958 increases lipogenesis and acts as a nanotherapeutic target in hepatocellular carcinoma [J].JOURNAL OF HEMATOLOGY & ONCOLOGY,2020,13(1).
APA：

Zuo Xueliang,Chen Zhiqiang,Gao Wen,Zhang Yao,&Wang Xuehao.(2020).M6A-mediated upregulation of LINC00958 increases lipogenesis and acts as a nanotherapeutic target in hepatocellular carcinoma .JOURNAL OF HEMATOLOGY & ONCOLOGY,13(1).
MLA：

Zuo Xueliang, et al. "M6A-mediated upregulation of LINC00958 increases lipogenesis and acts as a nanotherapeutic target in hepatocellular carcinoma" .JOURNAL OF HEMATOLOGY & ONCOLOGY 13,1(2020).
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