Long Noncoding RNA HCAL Facilitates the Growth and Metastasis of Hepatocellular Carcinoma by Acting as a ceRNA of LAPTM4B.
Long Noncoding RNA HCAL Facilitates the Growth and Metastasis of Hepatocellular Carcinoma by Acting as a ceRNA of LAPTM4B.
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长非编码 RNA HCAL 通过充当 LAPTM4B 的 ceRNA 促进肝细胞癌的生长和转移
DOI：
10.1016/j.omtn.2017.10.018
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发表时间：
2017-12-15
期刊：
影响因子：
--
通讯作者：
Yin ZY
中科院分区：
文献类型：
--
作者：
Xie CR;Wang F;Zhang S;Wang FQ;Zheng S;Li Z;Lv J;Qi HQ;Fang QL;Wang XM;Yin ZY
长链非编码RNA（lncRNAs）是一类新型的调控性非编码RNA。越来越多的证据表明，lncRNAs在肝细胞癌（HCC）的发生发展中起着关键作用。尽管已有几种lncRNAs得到注释，但大多数lncRNAs与HCC的关联仍不明确。在本研究中，我们通过进行lncRNA微阵列分析，探究了HCC中lncRNA的变化情况。我们鉴定出一种名为HCC相关lncRNA（HCAL）的新型lncRNA，其在HCC组织中高表达。HCAL的上调在临床上与HCC患者的低分化、血管内癌栓以及生存率降低相关。沉默HCAL在体外和体内均显著抑制HCC细胞的生长和转移。有趣的是，对HCAL敲低细胞的转录组测序分析显示，一些癌症相关通路发生了改变。从机制上讲，HCAL直接与miR - 15a、miR - 196a和miR - 196b等微小RNA（miRNA）相互作用并充当其分子海绵，从而调节溶酶体相关跨膜蛋白4B（LAPTM4B）的表达。综上所述，我们的研究结果表明，在HCC中存在一种新型的lncRNA - miRNA - mRNA调控网络，即HCAL - miR - 15a/miR - 196a/miR - 196b - LAPTM4B网络，并提示HCAL可能是治疗HCC的一个潜在靶点。
Long noncoding RNAs (lncRNAs) are a new class of regulatory noncoding RNAs. Emerging evidences indicate that lncRNAs play a critical role in the development of hepatocellular carcinoma (HCC). Although several lncRNAs have been annotated, the association of most lncRNAs with HCC is unknown. In this study, we investigated lncRNA alterations in HCC by performing lncRNA microarray analysis. We identified a novel lncRNA called HCC-associated lncRNA (HCAL) that was highly expressed in HCC tissues. HCAL upregulation was clinically associated with poor differentiation, intravascular cancer embolus, and decreased survival of patients with HCC. HCAL silencing significantly inhibited the growth and metastasis of HCC cells both in vitro and in vivo. Interestingly, transcriptome-sequencing analysis of HCAL-knockdown cells showed alterations in some cancer-related pathways. Mechanistically, HCAL directly interacted with and functioned as a sponge for microRNAs such as miR-15a, miR-196a, and miR-196b to modulate LAPTM4B expression. Taken together, our findings suggest the presence of a novel lncRNA-miRNA-mRNA regulatory network, i.e., the HCAL-miR-15a/miR-196a/miR-196b-LAPTM4B network, in HCC and indicate that HCAL may be a potential target for treating HCC.
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