LINC00114 promoted nasopharyngeal carcinoma progression and radioresistance in vitro and in vivo through regulating ERK/JNK signaling pathway via targeting miR-203

Y.-Y. Han, K. Liu, J. Xie, F. Li, Y. Wang, B. Yan

Department of Otolaryngology Head and Neck Surgery, Urumqi Eye and ENT Specialist Hospital, Urumqi, Xinjiang, China. xvkzel@163.com

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• Oncology

OBJECTIVE: 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.

MATERIALS AND METHODS: 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.

RESULTS: 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.

CONCLUSIONS: 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.

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