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LINC00958 通过调控 miR-627-5p/YBX2 轴促进口腔鳞状细胞癌的增殖和迁移。

LINC00958 regulated miR-627-5p/YBX2 axis to facilitate cell proliferation and migration in oral squamous cell carcinoma.

机构信息

Department of Stomatology, The Second Affiliated Hospital of Harbin Medical University , Harbin , China.

Department of Prosthodontics, The Second Affiliated Hospital of Harbin Medical University , Harbin , China.

出版信息

Cancer Biol Ther. 2019;20(9):1270-1280. doi: 10.1080/15384047.2019.1617571. Epub 2019 Jun 4.

Abstract

Oral squamous cell carcinoma (OSCC), the subtype of head and neck cancers, is notorious for its high incidence and death rate. The role of long non-coding RNAs (lncRNAs) is discovered to be significant for the canceration and cancer progression. Long intergenic non-protein coding RNA 958 (LINC00958) is discovered as a carcinogene in multiple cancers, such as gastric cancer, pancreatic cancer, and glioma, but there has been no report about how LINC00958 functions in OSCC. The objective of our study is to unfold function and mechanism investigation on LINC00958 in OSCC. First, TCGA database showed the upregulation and prognostic significance of LINC00958 in head and neck squamous carcinoma. Then, we discovered in OSCC clinical samples that LINC00958 presented high expression and predicted poor prognosis. Also, LINC00958 was elevated in OSCC cells. gain- and loss-function experiments proved that LINC00958 facilitated cell growth, retarded apoptosis, accelerated migration, and epithelial-to-mesenchymal transition (EMT) in OSCC. Mechanistically, we confirmed the cytoplasmic expression of LINC00958 in OSCC cells, and revealed that LINC00958 sequestered miR-627-5p to upregulate YBX2 expression. Rescue assays indicated that LINC00958 regulated OSCC cell proliferation, motility and EMT through YBX2. Together, we showed that LINC00958 promoted OSCC progression through miR-627-5p/YBX2 axis, indicating LINC00958 as a new prognostic marker, and provided new perspectives for molecular targeted treatment for OSCC.

摘要

口腔鳞状细胞癌(OSCC)是头颈部癌症的一种亚型,以其高发病率和死亡率而臭名昭著。长链非编码 RNA(lncRNA)的作用被发现对头颈癌的癌变和癌症进展具有重要意义。长链非编码 RNA 958(LINC00958)在多种癌症中被发现是一种致癌基因,如胃癌、胰腺癌和神经胶质瘤,但尚未有关于 LINC00958 在 OSCC 中作用的报道。本研究旨在揭示 LINC00958 在 OSCC 中的功能和机制。首先,TCGA 数据库显示 LINC00958 在头颈部鳞状细胞癌中的上调和预后意义。然后,我们在 OSCC 临床样本中发现 LINC00958 表达水平较高,且预测预后不良。此外,LINC00958 在 OSCC 细胞中也上调。Gain-和 loss-function 实验证明,LINC00958 促进 OSCC 细胞的生长、抑制凋亡、加速迁移和上皮-间充质转化(EMT)。在机制上,我们证实了 LINC00958 在 OSCC 细胞中的细胞质表达,并揭示了 LINC00958 通过与 miR-627-5p 结合来上调 YBX2 的表达。拯救实验表明,LINC00958 通过 YBX2 调节 OSCC 细胞的增殖、迁移和 EMT。综上所述,我们表明 LINC00958 通过 miR-627-5p/YBX2 轴促进 OSCC 进展,表明 LINC00958 作为一种新的预后标志物,为 OSCC 的分子靶向治疗提供了新的视角。

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