Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan.
Department of Frontier Science for Cancer and Chemotherapy, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan.
Int J Oncol. 2018 Feb;52(2):453-460. doi: 10.3892/ijo.2017.4218. Epub 2017 Dec 7.
Recent studies have indicated that long noncoding RNAs (lncRNAs) play a pivotal role in almost all physiological cellular processes, including every stage of cancer development. Given that hypoxia in the tumor microenvironment is involved in the malignant behavior of tumors, such as invasion and metastasis, we investigated the cytoplasmic and nuclear localization of lncRNAs in colorectal cancer cells. A cell culture under hypoxic conditions revealed several lncRNAs, such as LINC00152, whose levels were increased in the cytoplasm of colorectal cancer cells. A database study indicated that LINC00152 shares microRNA-binding sites, such as miR-138 and miR-193, with the hypoxia-inducible factor 1 (HIF1), thus suggesting that LINC00152 could possibly function as a competing endogenous RNA that can augment Hif1 translation in the cytoplasm of hypoxic colorectal cancer cells. Moreover, the data presented in the studies of surgically resected samples showed that patients with colorectal cancer exhibiting high LINC00152 expression were associated with a worsened survival rate; this supports the suggested oncogenic function of LINC00152 in the cytoplasm under hypoxic conditions. The present study demonstrated that lncRNA networks could provide diagnostic tools and novel therapeutic targets against colorectal cancer cells.
最近的研究表明,长非编码 RNA(lncRNA)在几乎所有生理细胞过程中发挥关键作用,包括癌症发展的各个阶段。鉴于肿瘤微环境中的缺氧与肿瘤的恶性行为有关,如侵袭和转移,我们研究了结直肠癌细胞中 lncRNA 的细胞质和核定位。在缺氧条件下培养的细胞显示出几种 lncRNA,如 LINC00152,其水平在结直肠癌细胞的细胞质中增加。数据库研究表明,LINC00152 与缺氧诱导因子 1(HIF1)共享 microRNA 结合位点,如 miR-138 和 miR-193,这表明 LINC00152 可能作为一种竞争性内源性 RNA,可在缺氧结直肠癌细胞的细胞质中增强 Hif1 翻译。此外,手术切除样本研究中提供的数据表明,结直肠癌患者中表达高 LINC00152 的患者生存率较差;这支持了 LINC00152 在缺氧条件下细胞质中的致癌功能。本研究表明,lncRNA 网络可以为结直肠癌细胞提供诊断工具和新的治疗靶点。