TPRG1-AS1 induces RBM24 expression and inhibits liver cancer progression by sponging miR-4691-5p and miR-3659
TPRG1-AS1 induces RBM24 expression and inhibits liver cancer progression by sponging miR-4691-5p and miR-3659
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DOI：
10.1111/liv.15026
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发表时间：
2021-08-08
影响因子：
6.7
通讯作者：
Woo, Hyun G.
中科院分区：
文献类型：
--
作者：
Choi, Ji-Hye;Kwon, So M.;Woo, Hyun G.
背景与目的非编码RNA(NcRNAs)在肝细胞癌的发生发展中起重要作用。在这里，通过进行RNA测序(RNA-Seq)分析，我们试图识别可能驱动肝癌异质性进展的新的ncRNA。方法获得68例肝癌组织和10例癌旁肝组织的RNA-Seq图谱。通过细胞实验评价潜在驱动因子ncRNAs的功能意义。结果TPRG1-AS1是促进肝癌异质性进展的潜在驱动非编码RNA。TPRG1-AS1诱导肿瘤抑制因子RNA结合基序蛋白24(RBM24)，通过激活凋亡的肿瘤细胞死亡来抑制肿瘤生长。此外，我们还报道了TPRG1-AS1作为RBM24的竞争内源RNA(CENA)，海绵miR-4691-5P和miR-3659以干扰它们与RBM24的结合。结论TPRG1-AS1是一种新的融合miR-4691-5p和miR-3659的Cerna，可诱导RBM24的表达，抑制肝癌生长。我们的结果为ncRNAs在异质性肝细胞癌进展中的作用提供了新的见解。
Background & Aims Noncoding RNAs (ncRNAs) play critical roles in hepatocellular carcinoma (HCC) progression. Here, by performing RNA-sequencing (RNA-Seq) profiling, we sought to identify novel ncRNAs that potentially drive the heterogeneous progression of liver cancers. Methods RNA-Seq profiles were obtained from 68 HCC specimens and 10 samples of adjacent non-tumour liver tissues. The functional significance of the potential driver ncRNAs was evaluated by cell experiments. Results TPRG1-AS1 was identified as a potential driver noncoding RNA that promotes heterogeneous liver cancer progression. TPRG1-AS1 induced tumour suppressor RNA-binding motif protein 24 (RBM24), suppressing tumour growth by activating apoptotic tumour cell death. In addition, we report that TPRG1-AS1 acts as a competing endogenous RNA (ceRNA) for RBM24, sponging miR-4691-5p and miR-3659 to interfere with their binding to RBM24. Conclusions We suggest that TPRG1-AS1 is a novel ceRNA sponging miR-4691-5p and miR-3659, resulting in RBM24 expression and suppression of liver cancer growth. Our results provide new insights into the functions of ncRNAs in heterogeneous HCC progression.