mascRNA and its parent lncRNA MALAT1 promote proliferation and metastasis of hepatocellular carcinoma cells by activating ERK/MAPK signaling pathway.
mascRNA and its parent lncRNA MALAT1 promote proliferation and metastasis of hepatocellular carcinoma cells by activating ERK/MAPK signaling pathway.
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mascRNA及其亲本lncRNA MALAT1通过激活ERK/MAPK信号通路促进肝细胞癌细胞的增殖和转移。
DOI：
10.1038/s41420-021-00497-x
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发表时间：
2021-05-17
影响因子：
7
通讯作者：
Zhang Q
中科院分区：
文献类型：
--
作者：
Xie SJ;Diao LT;Cai N;Zhang LT;Xiang S;Jia CC;Qiu DB;Liu C;Sun YJ;Lei H;Hou YR;Tao S;Hu YX;Xiao ZD;Zhang Q
MALAT 1相关小细胞质RNA（mascRNA）是源自核定位长非编码RNA（lncRNA）转移相关肺腺癌转录物1（MALAT 1）的细胞质tRNA样小RNA。虽然MALAT 1被广泛研究，并被发现在多个细胞过程中发挥作用，包括肿瘤发生和肿瘤进展，但mascRNA的作用在很大程度上是未知的。在这里，我们表明mascRNA在多种癌细胞系和肝细胞癌（HCC）临床样品中上调。以肝癌细胞为模型，我们发现mascRNA及其亲本lncRNA MALAT 1在体外均能促进细胞增殖、迁移和侵袭。相应地，两者均能促进小鼠皮下肿瘤模型的肿瘤生长，并通过尾静脉注射HCC细胞促进转移。此外，我们发现mascRNA和MALAT 1都可以激活ERK/MAPK信号通路，调节转移相关基因，并可能有助于HCC细胞的侵袭性表型。我们的研究结果表明，在HCC的发展和进展过程中，mascRNA和MALAT 1的功能和机制的协调，并提供了一个范例，在哺乳动物细胞中破译tRNA样结构及其亲本转录本。
MALAT1-associated small cytoplasmic RNA (mascRNA) is a cytoplasmic tRNA-like small RNA derived from nucleus-located long noncoding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1). While MALAT1 was extensively studied and was found to function in multiple cellular processes, including tumorigenesis and tumor progression, the role of mascRNA was largely unknown. Here we show that mascRNA is upregulated in multiple cancer cell lines and hepatocellular carcinoma (HCC) clinical samples. Using HCC cells as model, we found that mascRNA and its parent lncRNA MALAT1 can both promote cell proliferation, migration, and invasion in vitro. Correspondingly, both of them can enhance the tumor growth in mice subcutaneous tumor model and can promote metastasis by tail intravenous injection of HCC cells. Furthermore, we revealed that mascRNA and MALAT1 can both activate ERK/MAPK signaling pathway, which regulates metastasis-related genes and may contribute to the aggressive phenotype of HCC cells. Our results indicate a coordination in function and mechanism of mascRNA and MALAT1 during development and progress of HCC, and provide a paradigm for deciphering tRNA-like structures and their parent transcripts in mammalian cells.
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影响因子：
3.7
作者：
Ji Q;Liu X;Fu X;Zhang L;Sui H;Zhou L;Sun J;Cai J;Qin J;Ren J;Li Q
通讯作者：
Li Q
影响因子：
3.1
作者：
He, Meng;Shen, Juxin;Tao, Kelong
通讯作者：
Tao, Kelong
影响因子：
6
作者：
Chang, Hang-Lung;Bamodu, Oluwaseun Adebayo;Tsai, Jo-Ting
通讯作者：
Tsai, Jo-Ting
影响因子：
56.9
作者：
Kapranov, Philipp;Cheng, Jill;Gingeras, Thomas R.
通讯作者：
Gingeras, Thomas R.
影响因子：
56.9
作者：
Bertone, P;Stolc, V;Snyder, M
通讯作者：
Snyder, M