Department of Pathology, Saint Louis University, Saint Louis, MO, USA.
Department of Biology, Saint Louis University, Saint Louis, MO, USA.
EMBO Rep. 2020 Dec 3;21(12):e51042. doi: 10.15252/embr.202051042. Epub 2020 Oct 12.
Oral squamous cell carcinoma (OSCC) is the sixth most common cancer with a 5-year overall survival rate of 50%. Thus, there is a critical need to understand the disease process, and to identify improved therapeutic strategies. Previously, we found the long non-coding RNA (lncRNA) EGFR long non-coding downstream RNA (ELDR) induced in a mouse tongue cancer model; however, its functional role in human oral cancer remained unknown. Here, we show that ELDR is highly expressed in OSCC patient samples and in cell lines. Overexpression of ELDR in normal non-tumorigenic oral keratinocytes induces cell proliferation, colony formation, and PCNA expression. We also show that ELDR depletion reduces OSCC cell proliferation and PCNA expression. Proteomics data identifies the RNA binding protein ILF3 as an interacting partner of ELDR. We further show that the ELDR-ILF3 axis regulates Cyclin E1 expression and phosphorylation of the retinoblastoma (RB) protein. Intratumoral injection of ELDR-specific siRNA reduces OSCC and PDX tumor growth in mice. These findings provide molecular insight into the role of ELDR in oral cancer and demonstrate that targeting ELDR has promising therapeutic potential.
口腔鳞状细胞癌（OSCC）是第六种最常见的癌症，其 5 年总生存率为 50%。因此，迫切需要了解疾病的发生过程，并确定改善治疗策略。以前，我们在一个舌癌小鼠模型中发现长非编码 RNA（lncRNA）表皮生长因子受体长非编码下游 RNA（ELDR）诱导表达；然而，其在人口腔癌中的功能作用仍不清楚。在这里，我们表明 ELDR 在 OSCC 患者样本和细胞系中高度表达。ELDR 在正常非肿瘤性口腔角质形成细胞中的过表达诱导细胞增殖、集落形成和 PCNA 表达。我们还表明，ELDR 的缺失减少了 OSCC 细胞的增殖和 PCNA 的表达。蛋白质组学数据鉴定出 RNA 结合蛋白 ILF3 是 ELDR 的相互作用伙伴。我们进一步表明，ELDR-ILF3 轴调节细胞周期蛋白 E1 的表达和视网膜母细胞瘤（RB）蛋白的磷酸化。ELDR 特异性 siRNA 的肿瘤内注射减少了小鼠中的 OSCC 和 PDX 肿瘤生长。这些发现为 ELDR 在口腔癌中的作用提供了分子见解，并表明靶向 ELDR 具有有前途的治疗潜力。
