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Objective: LINC00114 could promote the development of colorectal cancer, but its mechanism has been rarely discussed in esophageal cancer (EC). Herein, we explored the molecular mechanism of LINC00114 via mediating enhancer of zeste homolog 2/deleted in liver cancer 1 (EZH2/DLC1) axis in EC. Methods: LINC00114, EZH2 and DLC1 expression in EC tissues and cells were tested. LINC00114, EZH2 and DLC1 expression were altered in EC cells through transfection with different constructs, and cell proliferation, migration, invasion, apoptosis and glycolysis were subsequently observed. The interaction between LINC00114 and EZH2 and that between EZH2 and DLC1 were explored. Tumor formation was also conducted to confirm the in vitro results. Results: The expression levels of LINC00114 and EZH2 were elevated while those of DLC1 were reduced in EC. Inhibiting LINC00114 or reducing EZH2 blocked cell proliferation, migration, invasion and glycolysis and induce cell apoptosis in EC. LINC00114 promoted H3K27 trimethylation of DLC1 by recruiting EZH2. Knockdown of DLC1 stimulated cell growth and glycolysis in EC and even mitigated the role of LINC00114 inhibition in EC. In vivo experiment further confirmed the anti-tumor effect of LINC00114 inhibition in EC. Conclusion: The data indicate that LINC00114 promotes the development of EC by recruiting EZH2 to enhance H3K27me3 of DLC1. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

This study aimed to identify the roles of the long non-coding RNA LINC00114 in colorectal cancer (CRC) development. The expression levels of LINC00114 and miR-133b in CRC were determined by reverse transcription (RT)-polymerase chain reaction (PCR) and the functions of LINC00114 in CRC were evaluated in vitro and in vivo. Methylation-specific PCR assay was performed to detect the miR-133b promoter methylation in CRC cells. Bioinformatics analysis, RNA immunoprecipitation, dual luciferase assay, RNA pull-down, co-immunoprecipitation (IP), and chromatin IP (ChIP) assays were used to elucidate whether LINC00114 could recruit EZH2/DNMT1 and bind to the miR-133b promoter region, leading to dysregulated methylation and the depression of miR-133b. The expression levels of DNA methyltransferases (DNMTs), EZH2, and nucleoporin 214(NUP214) were analyzed by western blotting. Data showed that LINC00114 was highly expressed, whereas miR-133b was downregulated in the CRC tissues and cells. In vitro, silencing LINC00114 inhibited cell proliferation and impeded cell cycle at the G1/S phase by upregulating miR-133b. In vivo, LINC00114 knockdown reduced tumor growth. Further analysis showed that the methylation in miR-133b promoter region was increased in the CRC and silencing LINC00114 increased miR-133b expression through depressing methylation of its promoter region. ChIP-PCR experiments demonstrated that EZH2 and DNMT1 could bind to the miR-133b promoter region and it was abolished by LINC00114 knockdown. sh-EZH2 reversed the overexpression of DNMTs and CRC cell cycle progression induced by the LINC00114 upregulation. LINC00114 could regulate the NUP214 protein expression by sponging miR-133b. These results demonstrated that LINC00114 suppressed miR-133b expression via EZH2/DNMT1-mediated methylation of its promoter region, indicating that LINC00114 might be a potential novel target for CRC diagnosis and treatment.