BACKGROUND Long noncoding RNAs (lncRNAs) are involved in the progression of various cancers and affect the response to radiotherapy. This study focused on clarifying the underlying mechanism by which lncTUG1 affects the radiosensitivity of esophageal squamous cell carcinoma (ESCC). METHODS lncTUG1, miR-144-3p and MET expression levels were detected in ESCC tissues and cells by qRT-PCR. Western blotting was used to examine the protein levels of MET, p-AKT and EGFR. The dual-luciferase reporter system and RNA immunoprecipitation (RIP) assays were used to confirm the interaction between lncTUG1 and miR-144-3p or miR-144-3p and MET. MTT, colony formation and flow cytometry assays were applied to examine the behavioral changes in EC9706 and KYSE30 cells. RESULTS lncTUG1 was upregulated in ESCC cells and tissues, and lncTUG1 expression was associated with an advanced pathological stage. The bioinformatics analysis revealed that lncTUG1 could specifically bind to miR-144-3p, which was downregulated in ESCC. There was a negative correlation between lncTUG1 and miR-144-3p. LncTUG1 inhibition retarded proliferation and colony formation and induced apoptosis in ESCC cells. Moreover, lncTUG1 knockdown dramatically improved the effect of radiotherapy on ESCC development both in vivo and in vitro. Furthermore, MET was revealed as a downstream target of miR-144-3p and is downregulated by it. LncTUG1 promoted the progression of ESCC and elevated radiotherapy resistance in ESCC cells, accompanied by a high level of MET expression. Moreover, we found that knockdown of lncTUG1 enhanced the radiosensitivity of ESCC cells via the p-AKT signaling pathway. CONCLUSION Our results indicate that lncTUG1 enhances the radiotherapy resistance of ESCC by lowering the miR-144-3p level and modulating the MET/EGFR/AKT axis.

中文翻译：

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lncTUG1 / miR-144-3p通过竞争性调节c-MET影响食管鳞状细胞癌的放射敏感性。

背景技术长的非编码RNA（lncRNA）参与各种癌症的发展，并影响对放射疗法的反应。这项研究的重点是弄清lncTUG1影响食管鳞状细胞癌（ESCC）放射敏感性的潜在机制。方法采用qRT-PCR方法检测ESCC组织和细胞中lncTUG1，miR-144-3p和MET的表达水平。使用蛋白质印迹法检测MET，p-AKT和EGFR的蛋白水平。使用双荧光素酶报告系统和RNA免疫沉淀（RIP）分析来确认lncTUG1与miR-144-3p或miR-144-3p与MET之间的相互作用。使用MTT，集落形成和流式细胞术测定来检查EC9706和KYSE30细胞的行为变化。结果lncTUG1在ESCC细胞和组织中上调，lncTUG1的表达与病理晚期有关。生物信息学分析表明，lncTUG1可以特异性结合在ESCC中下调的miR-144-3p。lncTUG1与miR-144-3p之间呈负相关。LncTUG1抑制抑制ESCC细胞的增殖和集落形成并诱导凋亡。此外，lncTUG1敲低显着改善了放射疗法在体内和体外对ESCC发育的影响。此外，MET被揭示为miR-144-3p的下游靶标，并被其下调。LncTUG1促进了ESCC的进展并提高了ESCC细胞的放射治疗抵抗力，并伴随着高水平的MET表达。而且，我们发现敲低lncTUG1通过p-AKT信号通路增强了ESCC细胞的放射敏感性。