Department of Radiotherapy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
School of Life Sciences, Zhengzhou University, Zhengzhou, Henan 450001, P.R. China.
Int J Oncol. 2021 Nov;59(5). doi: 10.3892/ijo.2021.5266. Epub 2021 Sep 17.
Increasing evidence has demonstrated that long non‑coding RNAs serve pivotal roles in tumor development, progression, metastasis and metabolism. However, to the best of our knowledge, the roles and molecular mechanisms of long intergenic nonprotein‑coding RNA 00514 (LINC00514) in esophageal squamous cell carcinoma (ESCC) remain unknown. The present study found that LINC00514 and sphingosine kinase 1 (SPHK1) were both upregulated in ESCC tissues and cells, and their high expression levels were closely associated with Tumor‑Node‑Metastasis stage, lymph node metastasis and poor prognosis of patients with ESCC. Functionally, knockdown of LINC00514 inhibited cell proliferation and invasion, and led to the downregulation of lipogenesis‑related proteins, including SPHK1, fatty acid synthase, acetyl‑coenzyme (Co)A carboxylase α and stearoyl‑CoA desaturase 1, whereas LINC00514 overexpression promoted cell proliferation and invasion in ESCC KYSE150 and KYSE30 cells, and upregulated expression of lipogenesis‑related proteins. Mechanistically, LINC00514 functioned as a competing endogenous RNA by sponging microRNA (miR)‑378a‑5p, resulting in the upregulation of SPHK1, which was accompanied by the activation of lipogenesis‑related pathways, to promote ESCC cell proliferation and invasion. Taken together, these findings suggest that LINC00514 may participate in ESCC lipogenesis, and targeting the LINC00514/miR‑378a‑5p/SPHK1 signaling axis may be a novel and promising therapeutic strategy for management of patients with ESCC.
越来越多的证据表明，长非编码 RNA 在肿瘤的发生、发展、转移和代谢中发挥关键作用。然而，就我们所知，长基因间非蛋白编码 RNA 00514（LINC00514）在食管鳞状细胞癌（ESCC）中的作用和分子机制尚不清楚。本研究发现，LINC00514 和鞘氨醇激酶 1（SPHK1）在 ESCC 组织和细胞中均上调，其高表达水平与肿瘤-淋巴结-转移分期、淋巴结转移和 ESCC 患者的预后不良密切相关。功能上，敲低 LINC00514 抑制细胞增殖和侵袭，并导致脂生成相关蛋白，包括 SPHK1、脂肪酸合酶、乙酰辅酶（Co）A 羧化酶 α 和硬脂酰-CoA 去饱和酶 1 的下调，而 LINC00514 过表达促进 ESCC KYSE150 和 KYSE30 细胞的增殖和侵袭，并上调脂生成相关蛋白的表达。机制上，LINC00514 通过海绵 microRNA（miR）-378a-5p 发挥竞争性内源性 RNA 的作用，导致 SPHK1 的上调，伴随着脂生成相关途径的激活，从而促进 ESCC 细胞的增殖和侵袭。综上所述，这些发现表明 LINC00514 可能参与 ESCC 的脂生成，靶向 LINC00514/miR-378a-5p/SPHK1 信号轴可能是管理 ESCC 患者的一种新的有前途的治疗策略。
