LncRNA-TUSC7/miR-224 affected chemotherapy resistance of esophageal squamous cell carcinoma by competitively regulating DESC1.
LncRNA-TUSC7/miR-224 affected chemotherapy resistance of esophageal squamous cell carcinoma by competitively regulating DESC1.
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LncRNA-TUSC7/miR-224通过竞争性调节DESC1影响食管鳞癌化疗耐药
DOI：
10.1186/s13046-018-0724-4
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发表时间：
2018-03-12
期刊：
影响因子：
--
通讯作者：
Qin YR
中科院分区：
文献类型：
--
作者：
Chang ZW;Jia YX;Zhang WJ;Song LJ;Gao M;Li MJ;Zhao RH;Li J;Zhong YL;Sun QZ;Qin YR
本研究旨在阐明LNC TUSC7在食管鳞癌化疗耐药中的作用机制。方法采用定量RT-PCR方法检测TUSC7、miR-224和DESC1在食管鳞癌组织和细胞中的表达。Western印迹法检测DESC1、EGFR和p-AKT的蛋白表达。采用Kaplan-Meier方法计算总存活率。用双荧光素酶报告基因检测和RIP检测证实TUSC7与miR-224结合，miR-224与DESC1结合。结果TUSC7在食管鳞癌组织和细胞中表达下调，TUSC7表达水平越低，总生存率越低。生物信息学软件分析表明，TUSC7与miR-224特异性结合，证明miR-224在ESCC中高表达，且与TUSC7表达呈负相关。过表达TUSC7/抑制miR-224可抑制ESCC细胞的增殖、集落形成和化疗耐药性，促进细胞凋亡。此外，我们还证实了miR-224与DESC1特异结合，并与DESC1呈负相关。TUSC7通过抑制miR-224而上调DESC1的表达，从而抑制食管癌细胞的增殖和化疗耐药。我们还证实了DESC1通过EGFR/AKT抑制了ESCC细胞的化疗耐药。结论TUSC7可能通过下调miR-224，调节DESC1/EGFR/AKT通路，从而抑制食管癌的化疗耐药性。
BackgroundThis study aims to clarify the underlying mechanism for the tumor suppressive function of lnc TUSC7 in chemotherapy resistance of esophageal squamous cell carcinoma (ESCC).MethodsTUSC7, miR-224 and DESC1 expressions in ESCC tissues and cells were detected by qRT-PCR. Protein level of DESC1, EGFR and p-AKT were observed by Western blot. Overall survival was calculated using the Kaplan-Meier method. Dual-luciferase reporter gene assay and RIP assay were used to comfirm TUSC7 binding to miR-224, and miR-224 binding to DESC1. Cell proliferation, apoptosis, and colony formation was detected by MTT, Flow Cytometry and Colony formation assays.ResultsTUSC7 was downregulated in ESCC tissues and cells, and low TUSC7 indicated worse overall survival. The analysis of bioinformatics softwares showed that TUSC7 specifically bound to miR-224, and we proved miR-224 was upregulated in ESCC and negatively correlated with TUSC7 expression. Overexpression of TUSC7/inhibition of miR-224 suppressed cell proliferation, colony formation and chemotherapy resistance of ESCC cells, and promoted cell apoptosis. In addition, we confirmed that miR-224 specifically bound to DESC1, and negatively correlated with DESC1. TUSC7 suppressed the proliferation and chemotherapy resistance of ESCC cells by increasing DESC1 expression via inhibiting miR-224. We also confirmed DESC1 inhibited chemotherapy resistance of ESCC cells via EGFR/AKT. Finally, in vivo experiments demonstrated that overexpression of TUSC7 decreased tumor growth and chemotherapy resistance.ConclusionThese findings suggested TUSC7 suppressed chemotherapy resistance of ESCC by downregulating miR-224 to modulate DESC1/EGFR/AKT pathway.
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影响因子：
--
作者：
Cui R;Kim T;Fassan M;Meng W;Sun HL;Jeon YJ;Vicentini C;Tili E;Peng Y;Scarpa A;Liang G;Zhang YK;Chakravarti A;Croce CM
通讯作者：
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3
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
6.4
作者：
Qi, Peng;Xu, Mi-die;Du, Xiang
通讯作者：
Du, Xiang