Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Hepato‑Pancreato‑Biliary Surgery, Peking University Cancer Hospital and Institute, Beijing 100142, P.R. China.
MOE Key Lab, Bioinformatics, School of Life Sciences, Tsinghua University, Beijing 100084, P.R. China.
Mol Med Rep. 2022 Feb;25(2). doi: 10.3892/mmr.2022.12587. Epub 2022 Jan 11.
Long non‑coding RNAs can regulate the malignant tumor phenotype either as tumor suppressors or oncogenes. The present study investigated the underlying mechanism of LINC00238 in liver cancer. LINC00238 was identified as a downregulated molecule in The Cancer Genome Atlas liver hepatocellular carcinoma dataset through Gene Expression Profiling Interactive Analysis software. Through gain‑ and loss‑of‑function experiments, LINC00238 was confirmed as a tumor suppressor that could not only decrease cell viability, migration and invasion , but also tumorigenesis and tumor metastasis . By cytoplasmic and nuclear RNA isolation, LINC00238 was confirmed to be predominantly cytoplasmic. Mechanistically, RNA pull‑down assays showed that LINC00238 sponged microRNA (miR)‑522 and then reversed the inhibitory effects on two downstream targets, secreted frizzled related protein 2 and dickkopf1. Collectively, LINC00238 was identified as a tumor suppressor that acts via sponging miR‑522 followed by silencing of downstream targets, suggesting that LINC00238 may have a key role in suppressing the malignant phenotype of liver cancer cells.
长链非编码 RNA 可以作为肿瘤抑制因子或癌基因来调节恶性肿瘤表型。本研究探讨了 LINC00238 在肝癌中的潜在机制。通过 Gene Expression Profiling Interactive Analysis 软件,在 The Cancer Genome Atlas 肝癌数据集鉴定 LINC00238 为下调分子。通过 gain-和 loss-功能实验,证实 LINC00238 是一种肿瘤抑制因子,不仅可以降低细胞活力、迁移和侵袭,还可以抑制肿瘤发生和转移。通过细胞质和核 RNA 分离,证实 LINC00238 主要位于细胞质中。机制上,RNA 下拉实验表明,LINC00238 可以吸附 microRNA(miR)-522,然后逆转对两个下游靶标分泌卷曲相关蛋白 2 和 dickkopf1 的抑制作用。总之,LINC00238 被鉴定为一种肿瘤抑制因子,通过吸附 miR-522 然后沉默下游靶标发挥作用,表明 LINC00238 可能在抑制肝癌细胞的恶性表型中起关键作用。