Department of Otolaryngology Head and Neck Surgery, Urumqi Eye and ENT Specialist Hospital, Urumqi, Xinjiang, China.
Eur Rev Med Pharmacol Sci. 2020 Mar;24(5):2491-2504. doi: 10.26355/eurrev_202003_20517.
Nasopharyngeal carcinoma (NPC) is a malignancy and is prone to distant metastasis and radioresistance. Long non-coding RNAs (lncRNAs) play vital roles in human cancers. The purpose of this study was to explore the role and the action mechanism of intergenic lncRNA (LINC00114) in NPC.
The expression of LINC00114 and microRNA-203 (miR-203) was measured by quantitative real-time polymerase chain reaction (qRT-PCR). NPC cells were exposed to X-ray as radiation treatment. Cell proliferation, migration, cell survival fraction and apoptosis were assessed by 3-(4, 5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT), transwell, colony formation, and flow cytometry assays, respectively. The expression of Cleaved-cas-3, Cleaved-cas-9, phosphor-ERK (p-ERK) and phosphor-JNK (p-JNK) was quantified by Western blot. The interaction between miR-203 and LINC00114 was predicted by bioinformatics tool microRNA.org and verified by dual-luciferase reporter assay. Tumor formation assay in nude mice was conducted to examine the role of LINC00114 in vivo.
LINC00114 was upregulated in serums from NPC patients, tissues and cell lines of NPC. LINC00114 knockdown inhibited proliferation, migration, and radioresistance of NPC cells. MiR-203 was a target of LINC00114, and miR-203 inhibition eliminated the effects of LINC00114 knockdown. Besides, the extracellular signal-regulated kinases (ERK)/c-Jun N-terminal kinases (JNK) pathway was inactivated by LINC00114 knockdown but recovered by miR-203 inhibition. Moreover, LINC00114 knockdown suppressed tumor growth and radioresistance in vivo.
LINC00114 contributed to NPC development and radioresistance through the regulation of ERK/JNK signaling pathway and the mediation of miR-203, suggesting that LINC00114 was a promising biomarker to defense NPC progression and radioresistance.
鼻咽癌（NPC）是一种恶性肿瘤，易发生远处转移和放射抵抗。长链非编码 RNA（lncRNA）在人类癌症中发挥重要作用。本研究旨在探讨基因间 lncRNA（LINC00114）在 NPC 中的作用和作用机制。
通过实时定量聚合酶链反应（qRT-PCR）测量 LINC00114 和 microRNA-203（miR-203）的表达。用 X 射线照射 NPC 细胞作为放射治疗。通过 3-(4,5-二甲基-2-噻唑基)-2,5-二苯基-2-H-四唑溴盐（MTT）、transwell、集落形成和流式细胞术分别评估细胞增殖、迁移、细胞存活分数和细胞凋亡。通过 Western blot 定量测定 Cleaved-cas-3、Cleaved-cas-9、磷酸化 ERK（p-ERK）和磷酸化 JNK（p-JNK）的表达。通过生物信息学工具 microRNA.org 预测 miR-203 和 LINC00114 之间的相互作用，并通过双荧光素酶报告基因 assay 验证。在裸鼠体内进行肿瘤形成实验，以研究 LINC00114 在体内的作用。
LINC00114 在 NPC 患者血清、组织和细胞系中上调。LINC00114 敲低抑制 NPC 细胞的增殖、迁移和放射抵抗。miR-203 是 LINC00114 的靶标，miR-203 抑制消除了 LINC00114 敲低的影响。此外，LINC00114 敲低可使细胞外信号调节激酶（ERK）/c-Jun N 末端激酶（JNK）通路失活，但 miR-203 抑制可恢复该通路。此外，LINC00114 敲低可抑制体内肿瘤生长和放射抵抗。
LINC00114 通过调节 ERK/JNK 信号通路和 miR-203 的介导促进 NPC 的发生和放射抵抗，提示 LINC00114 是防御 NPC 进展和放射抵抗的有前途的生物标志物。
