Medical Faculty of Kunming University of Science and Technology, Kunming, Yunnan, China.
Department of Ophthalmology, The Affiliated Hospital of Kunming University of Science and Technology, The First People's Hospital of Yunnan Province, Kunming, Yunnan, China.
Tumori. 2023 Feb;109(1):28-37. doi: 10.1177/03008916211072585. Epub 2022 Feb 9.
Long non-coding RNAs have been implicated in various cancers as they regulate critical cellular processes such as proliferation, migration, invasion, and apoptosis in tumorous tissues. lncRNA-PNUTS is newly reported as an alternatively-spliced lncRNA from PNUTS pre-mRNA that promotes oncogenesis in breast cancer. However, whether LncRNA-PNUTS plays a role in other forms of cancers, such as liver cancer, remains unknown.
In the current study, we investigated the potential role of lncRNA-PNUTS in hepatocellular carcinoma (HCC). The levels of lncRNA-PNUTS in tumorous tissues obtained from HCC patients were measured. The potential impacts of lncPNUTS on metastasis and invasion were investigated through gain- or loss- of function experiments in cell models of liver cancers, as well as other cellular assays such as trans-well assays and wound-healing assays.
Here, we report that lncPNUTS was upregulated in human HCC tissues. Loss- and gain-of-function experiments indicated lncPNUTS promoted metastasis and invasion. In addition, ZEB1, which is involved in the activation of epithelial-mesenchymal-transition (EMT), was identified as a downstream target of lncPNUTS.
Our findings indicated lncPNUTS promotes HCC cancer cell metastasis and invasion via targeting ZEB1 to activate the EMT pathway, suggesting that lncPNUTS is a potential prognostic marker and therapeutic target for HCC patients.
长链非编码 RNA （lncRNA）在各种癌症中都有涉及，因为它们在肿瘤组织中调节着关键的细胞过程，如增殖、迁移、侵袭和凋亡。lncRNA-PNUTS 是一种新报道的从 PNUTS 前体 mRNA 中剪接的 lncRNA，可促进乳腺癌的发生。然而，lncRNA-PNUTS 是否在其他形式的癌症（如肝癌）中发挥作用尚不清楚。
在本研究中，我们研究了 lncRNA-PNUTS 在肝细胞癌（HCC）中的潜在作用。测定了来自 HCC 患者肿瘤组织中的 lncRNA-PNUTS 水平。通过在肝癌细胞模型以及其他细胞实验（如 Transwell 实验和划痕愈合实验）中进行的功能获得或缺失实验，研究了 lncPNUTS 对转移和侵袭的潜在影响。
我们报告称，lncPNUTS 在人 HCC 组织中上调。功能获得和缺失实验表明 lncPNUTS 促进了转移和侵袭。此外，ZEB1 作为上皮间质转化（EMT）激活的一个关键调节因子，被鉴定为 lncPNUTS 的下游靶标。
我们的研究结果表明，lncPNUTS 通过靶向 ZEB1 激活 EMT 通路促进 HCC 癌细胞的转移和侵袭，提示 lncPNUTS 是 HCC 患者潜在的预后标志物和治疗靶点。
