Long Noncoding RNA PVT1 Promotes Non-Small Cell Lung Cancer Cell Proliferation through Epigenetically Regulating LATS2 Expression
Long Noncoding RNA PVT1 Promotes Non-Small Cell Lung Cancer Cell Proliferation through Epigenetically Regulating LATS2 Expression
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长非编码 RNA PVT1 通过表观遗传调节 LATS2 表达促进非小细胞肺癌细胞增殖。
DOI：
10.1158/1535-7163.mct-15-0707
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发表时间：
2016-05-01
影响因子：
5.7
通讯作者：
Wang, Zhao-Xia
中科院分区：
文献类型：
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作者：
Wan, Li;Sun, Ming;Wang, Zhao-Xia
长链非编码RNA（longnoncodingRNA，lncRNA）是一类不编码蛋白质的新型转录物，在肿瘤细胞增殖、凋亡和转移中具有多种功能。lncRNA PVT 1的长度为1，716 nt，位于chr8q24.21区域，该区域还包含髓细胞瘤病（MYC）癌基因。先前的研究表明，MYC促进原发性人类癌症中PVT 1的表达。然而，PVT 1在非小细胞肺癌（NSCLC）中的表达模式和潜在的生物学功能尚不清楚。在这里，我们发现PVT 1在105例人类NSCLC组织中与正常样本相比上调。PVT 1的高表达与较高的肿瘤淋巴结转移分期和肿瘤大小以及较差的总生存期相关。功能分析表明，PVT 1基因敲低抑制NSCLC细胞增殖，并诱导凋亡，在体外和体内。RNA免疫沉淀和染色质免疫沉淀分析表明，PVT 1招募EZH 2的大肿瘤抑制激酶2（LATS 2）启动子和抑制LATS 2的转录。此外，LATS 2的异位表达通过调节Mdm 2-p53通路增加了细胞凋亡并抑制了肺腺癌细胞的增殖。因此，PVT 1/EZH 2/LATS 2相互作用可能成为肺腺癌诊断和治疗的新靶点。(C)2016年AACR。
Long noncoding RNAs (lncRNA) are a novel class of transcripts with no protein coding capacity, but with diverse functions in cancer cell proliferation, apoptosis, and metastasis. The lncRNA PVT1 is 1,716 nt in length and located in the chr8q24.21 region, which also contains the myelocytomatosis (MYC) oncogene. Previous studies demonstrated that MYC promotes PVT1 expression in primary human cancers. However, the expression pattern and potential biologic function of PVT1 in non-small cell lung cancer (NSCLC) is still unclear. Here, we found that PVT1 was upregulated in 105 human NSCLC tissues compared with normal samples. High expression of PVT1 was associated with a higher tumor-node-metastasis stage and tumor size, as well as poorer overall survival. Functional analysis revealed that knockdown of PVT1 inhibited NSCLC cell proliferation and induced apoptosis both in vitro and in vivo. RNA immunoprecipitation and chromatin immunoprecipitation assays demonstrated that PVT1 recruits EZH2 to the large tumor suppressor kinase 2 (LATS2) promoter and represses LATS2 transcription. Furthermore, ectopic expression of LATS2 increased apoptosis and repressed lung adenocarcinoma cell proliferation by regulating the Mdm2-p53 pathway. Taken together, our findings indicated that PVT1/EZH2/LATS2 interactions might serve as new target for lung adenocarcinoma diagnosis and therapy. (C) 2016 AACR.