BACKGROUND & AIMS: BACKGROUND AND AIM:The miR-196a2 gene contains a C/T polymorphism (rs11614913). Its presence could change the conformation of secondary structure of miR-196a2 RNA, and directly affect the binding to target mRNAs and the miRNA maturation process. Both of which eventually alter protein expression and contributed to cancer susceptibility. This study assessed whether the rs11614913 single nucleotide polymorphism (SNP) could affect an individual's susceptibility to esophageal squamous cell carcinomas (ESCC). METHODS:SNP rs11614913 was genotyped by polymerase chain reaction ligase detection reaction (PCR-LDR) in 597 ESCC patients and 597 control subjects. RESULTS:Overall, there were no significant differences in the frequency of the miRNA-196a2 SNP rs11614913 genotype between the ESCC cases and the controls (χ(2) = 1.395, p = 0.498). The TT genotype, CT genotype and CT/TT combined genotype (dominant model) did not modify the risk of ESCC as compared with the CC genotype. Comparisons of the TT genotype to the CT/CC combined genotype did not reveal a significant association to ESCC, too. However, further analyses revealed an increased risk of ESCC in the dominant model (OR = 1.56, 95% CI = 1.08-2.26) and the allele frequency comparison (OR = 1.31, 95% CI = 1.06-1.63) in the ≤60-year-old group. CONCLUSIONS:These results suggest that the miRNA-196a2 functional polymorphism rs11614913 might be an effective genetic marker for ESCC risk assessment in individuals younger than 60 years of age from a region of high ESCC incidence in northern China.

背景与目标： 背景与目的：miR-196a2基因具有C / T多态性（rs11614913）。它的存在可以改变miR-196a2 RNA二级结构的构象，并直接影响与靶mRNA的结合以及miRNA的成熟过程。两者最终都会改变蛋白质表达，并导致癌症易感性。这项研究评估了rs11614913单核苷酸多态性（SNP）是否会影响个体对食道鳞状细胞癌（ESCC）的敏感性。
方法：采用聚合酶链反应-连接酶检测反应（PCR-LDR）对597例ESCC患者和597例对照者进行SNP rs11614913基因分型。
结果：总体上，ESCC病例与对照组之间的miRNA-196a2 SNP rs11614913基因型频率没有显着差异（χ（2）= 1.395，p = 0.498）。与CC基因型相比，TT基因型，CT基因型和CT / TT组合基因型（优势模型）没有改变ESCC的风险。 TT基因型与CT / CC组合基因型的比较也没有显示出与ESCC的显着关联。然而，进一步的分析显示，在主导模型中，食管癌的风险增加（OR = 1.56，95％CI = 1.08-2.26），等位基因频率比较（OR = 1.31，95％CI = 1.06-1.63）在≤60-岁的组。
结论：这些结果表明，miRNA-196a2功能多态性rs11614913可能是中国北方地区ESCC高发地区60岁以下人群进行ESCC风险评估的有效遗传标记。

BACKGROUND & AIMS: BACKGROUND:Increased reactive oxygen species (ROS) production by arsenic treatment in solid tumors showed to be effective to sensitize cancer cells to chemotherapies. Arsenic nano compounds are known to increase the ROS production in solid tumors. METHODS:In this study we developed arsenic-ferrosoferric oxide conjugated Nano Complex (As2S2-Fe3O4, AFCNC) to further promote the ROS induction ability of arsenic reagent in solid tumors. We screen for the molecular pathways that are affect by arsenic treatment in ESCC cancer cells. And explored the underlying molecular mechanism for the arsenic mediated degradations of the key transcription factor we identified in the gene microarray screen. Mouse xenograft model were used to further verify the synthetic effects of AFCNC with chemo and radiation therapies, and the molecular target of arsenic treatment is verified with IHC analysis. RESULTS:With gene expression microarray analysis we found Hippo signaling pathway is specifically affected by arsenic treatment, and induced ubiquitination mediated degradation of YAP in KYSE-450 esophageal squamous cell carcinoma (ESCC) cells. Mechanistically we proved PML physically interacted with YAP, and arsenic induced degradation PML mediated the degradation of YAP in ESCC cells. As a cancer stem cell related transcription factor, YAP 5SA over expressions in cancer cells are correlated with resistance to chemo and radiation therapies. We found AFCNC treatment inhibited the increased invasion and migration ability of YAP 5SA overexpressing KYSE-450 cells. AFCNC treatment also effectively reversed protective effects of YAP 5SA overexpression against cisplatin induced apoptosis in KYSE-450 cells. Lastly, with ESCC mouse xenograft model we found AFCNC combined with cisplatin treatment or radiation therapy significantly reduced the tumor volumes in vivo in the xenograft ESCC tumors. CONCLUSIONS:Together, these findings suggested besides ROS, YAP is a potential target for arsenic based therapy in ESCC, which should play an important role in the synthetic effects of arsenic nano complex with chemo and radiation therapy.

背景与目标： 背景：在实体瘤中通过砷处理增加了活性氧（ROS）的产生，可有效地使癌细胞对化学疗法敏感。已知砷纳米化合物会增加实体瘤中的ROS产生。
方法：在这项研究中，我们开发了砷-铁-铁氧化物共轭纳米复合物（As2S2-Fe3O4，AFCNC），以进一步增强砷剂在实体瘤中的ROS诱导能力。我们筛选了受砷治疗的ESCC癌细胞中影响的分子途径。并探索了我们在基因芯片筛选中鉴定的关键转录因子的砷介导降解的潜在分子机制。使用小鼠异种移植模型进一步验证化学疗法和放射疗法对AFCNC的合成作用，并通过IHC分析验证了砷治疗的分子靶标。
结果：通过基因表达微阵列分析，我们发现了Hippo信号通路受到砷处理的特异性影响，并在KYSE-450食管鳞癌（ESCC）细胞中诱导了泛素化介导的YAP降解。从机理上讲，我们证明了PML与YAP发生了物理相互作用，并且砷诱导的降解PML介导了ESCC细胞中YAP的降解。作为与癌症干细胞相关的转录因子，YAP 5SA在癌细胞中的过度表达与对化学疗法和放射疗法的抵抗力相关。我们发现AFCNC处理抑制了过表达KYSE-450细胞的YAP 5SA的增加的侵袭和迁移能力。 AFCNC处理还有效逆转了YAP 5SA过表达对KYSE-450细胞中顺铂诱导的细胞凋亡的保护作用。最后，在ESCC小鼠异种移植模型中，我们发现AFCNC与顺铂治疗或放射治疗相结合可显着降低异种移植ESCC肿瘤的体内肿瘤体积。
结论：这些发现提示，除ROS外，YAP还可能成为ESCC砷基治疗的潜在靶标，这在化学和放射治疗砷纳米复合物的合成作用中应发挥重要作用。

BACKGROUND & AIMS: :S-adenosylhomocysteine hydrolase (SAHH) is the sole enzyme that catalyses the hydrolysis of S-adenosylhomocysteine (SAH) in methylation reaction. Previous studies have shown that its inhibition or deficiency leads to several human disorders such as severe coagulopathy, hepatopathy and myopathy. However, the effects of SAHH on esophageal squamous cell carcinoma (ESCC) cells have not been explored so far. To determine whether SAHH is involved in carcinogenesis of the esophagus, we investigated the expression of SAHH in ESCC and normal esophageal epithelial cells and found that SAHH was downregulated in ESCC cells compared with normal esophageal epithelial cells (P < 0.05). The overexpressed SAHH in ESCC cells promoted cell apoptosis, inhibited cell migration and adhesion, but did not affect the cell proliferation and cell cycle. Furthermore, an interaction of SAHH with receptor of activated C kinase 1 (RACK1) protein was detected by coimmunoprecipitation and an increased RACK1, which is caused by overexpression of SAHH, was verified by Western blotting. The findings mentioned above demonstrate that SAHH can promote apoptosis, inhibit migration and adhesion of ESCC cells suggesting that it may be involved in carcinogenesis of the esophagus.

背景与目标： ：S-腺苷同型半胱氨酸水解酶（SAHH）是在甲基化反应中催化S-腺苷同型半胱氨酸（SAH）水解的唯一酶。先前的研究表明，其抑制或缺乏会导致多种人类疾病，例如严重的凝血病，肝病和肌病。但是，到目前为止，尚未探讨SAHH对食道鳞状细胞癌（ESCC）细胞的作用。为了确定SAHH是否与食道癌发生有关，我们调查了SAHH在ESCC和正常食管上皮细胞中的表达，发现与正常食管上皮细胞相比SAHH在ESCC细胞中下调（P <0.05）。在ESCC细胞中过表达的SAHH促进细胞凋亡，抑制细胞迁移和粘附，但不影响细胞增殖和细胞周期。此外，通过免疫共沉淀检测到SAHH与活化的C激酶1（RACK1）蛋白受体之间的相互作用，并通过Western印迹法证实了SAHH过表达引起的RACK1增加。上面提到的发现表明SAHH可以促进细胞凋亡，抑制ESCC细胞的迁移和粘附，表明它可能与食道的癌变有关。

BACKGROUND & AIMS: BACKGROUND:The XRCC6 and XRCC5 genes are part of the nonhomologous end-joining (NHEJ) pathway, which is the main mechanism repairing DNA double-strand breaks (DSBs) in human cells. Genetic variations of XRCC6 and XRCC5 might contribute to esophageal squamous cell carcinoma (ESCC) susceptibility. METHODS:ESCC patients (n = 189) and cancer-free controls (n = 189) were recruited in an ESCC high-risk area of north China. Then the rs2267437 (XRCC6), rs3835 (XRCC5) and rs16855458 (XRCC5) polymorphisms were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. RESULTS:A significant difference in genotype distribution and allele frequency of rs2267437 (XRCC6) was observed between the cases and controls. The CG carriers were at higher risk of ESCC (p = 0.001, odds ratio [OR] = 2.040, 95% confidence interval [95% CI], 1.323-3.147). G allele carriers were also associated with an increased ESCC risk (p = 0.003, OR = 1.868, 95% CI, 1.230-2.836). In the 2 polymorphisms of XRCC5, no significant difference was found between both groups in the distribution of either genotype or allelic frequency. But in the haplotypes established by the single nucleotide polymorphisms (SNPs) of XRCC5, the haplotype AT and CC separately increased by 4.28- and 2.31-fold the risk ratio of ESCC (p = 0.01, OR = 4.28, 95% CI, 1.40-13.05; p = 0.03, OR = 2.31, 95% CI, 1.11-4.80, respectively). In addition, gene-smoking or gene-drinking interactions, and their effect on the risk of ESCC were observed, but no significant gene-environment interaction was demonstrated. CONCLUSIONS:In conclusion, both the CG carriers/G allele carriers of rs2267437 (XRCC6) and the haplotype AT/CC established by the SNPs of XRCC5 are associated with ESCC susceptibility.

背景与目标： 背景：XRCC6和XRCC5基因是非同源末端连接（NHEJ）途径的一部分，该途径是修复人类细胞中DNA双链断裂（DSB）的主要机制。 XRCC6和XRCC5的遗传变异可能有助于食管鳞状细胞癌（ESCC）的易感性。
方法：在中国北方的ESCC高危地区招募ESCC患者（189例）和无癌对照（189例）。然后使用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）分析对rs2267437（XRCC6），rs3835（XRCC5）和rs16855458（XRCC5）多态性进行基因分型。
结果：病例与对照组之间的rs2267437（XRCC6）基因型分布和等位基因频率存在显着差异。 CG携带者罹患食管鳞癌的风险较高（p = 0.001，优势比[OR] = 2.040，95％置信区间[95％CI]，1.323-3.147）。 G等位基因携带者也与ESCC风险增加相关（p = 0.003，OR = 1.868，95％CI，1.230-2.836）。在XRCC5的2个多态性中，两组在基因型或等位基因频率的分布上均未发现显着差异。但是在由XRCC5的单核苷酸多态性（SNP）建立的单倍型中，单倍型AT和CC分别增加了ESCC风险比的4.28和2.31倍（p = 0.01，OR = 4.28，95％CI，1.40- 13.05； p = 0.03，OR = 2.31，95％CI，1.11-4.80）。此外，观察到基因吸烟或基因饮用相互作用，以及它们对ESCC风险的影响，但未显示出显着的基因-环境相互作用。
结论：总之，rs2267437（XRCC6）的CG携带者/ G等位基因携带者和XRCC5的SNPs建立的单倍型AT / CC均与ESCC易感性相关。

BACKGROUND & AIMS: :The transforming growth factor β (TGF-β) signaling pathway plays anti- and pro-tumoral roles in the vast majority of cancers, and long noncoding RNAs have been reported to play key roles in the highly contextual response process. However, the roles of long noncoding RNAs (lncRNAs) in TGF-β signaling in esophageal squamous cell carcinoma (ESCC) remain unknown. In this study, we performed RNA-seq to compare lncRNAs expression levels between TGF-β1-treated and untreated ESCC cells and observed that NF-kappaB-interacting lncRNA (NKILA) was remarkably upregulated by the classical TGF-β signaling pathway. RNA profiling of 39 pairs ESCC tumor and adjacent nontumor samples using RT-qPCR demonstrated that NKILA is significantly downregulated in ESCC tumor tissues, and NKILA expression levels were significantly decreased in advanced tumor tissues (III and IV) compared to early stages (I and II) (p < 0.01). Gain- and loss-of-function assays showed that NKILA inhibited ESCC cell metastasis in vitro and in vivo, and mechanism studies showed that NKILA repressed MMP14 expression by inhibiting IκBα phosphorylation and NF-κB activation. Collectively, these findings suggest that the TGF-β-induced lncRNA NKILA has potential as an antimetastasis therapy. KEY MESSAGES:Long noncoding RNA NKILA could be remarkably upregulated by classical TGF-β signal pathway in ESCC. NKILA was significantly downregulated in esophageal squamous cell carcinoma and negatively correlated with TNM stage. NKILA inhibits ESCC cell metastasis via repressing MMP14 expression by suppressing the phosphorylation of IκBα and NF-κB activation.

背景与目标： ：转化生长因子β（TGF-β）信号通路在绝大多数癌症中均具有抗肿瘤和促肿瘤作用，据报道，长的非编码RNA在高度相关的反应过程中起关键作用。然而，在食管鳞状细胞癌（ESCC）中，长非编码RNA（lncRNA）在TGF-β信号传导中的作用仍然未知。在这项研究中，我们进行了RNA序列比较以比较TGF-β1处理和未处理的ESCC细胞之间的lncRNA表达水平，并观察到NF-κB相互作用的lncRNA（NKILA）被经典的TGF-β信号通路显着上调。使用RT-qPCR对39对ESCC肿瘤和邻近非肿瘤样品进行RNA谱分析表明，与早期阶段（I和II）相比，NKILA在ESCC肿瘤组织中显着下调，并且在晚期肿瘤组织（III和IV）中NKILA表达水平显着降低）（p <0.01）。功能获得和丧失功能测定显示NKILA在体内外均抑制ESCC细胞转移，机理研究表明NKILA通过抑制IκBα磷酸化和NF-κB活化来抑制MMP14表达。总的来说，这些发现表明TGF-β诱导的lncRNA NKILA具有作为抗转移疗法的潜力。
关键信息：ESCC中的经典TGF-β信号通路可能显着上调了长非编码RNA NKILA。 NKILA在食管鳞状细胞癌中显着下调，与TNM分期呈负相关。 NKILA通过抑制IκBα的磷酸化和NF-κB的活化来抑制MMP14的表达，从而抑制ESCC细胞的转移。

BACKGROUND & AIMS: :NF45 (also known as ILF2), as one subunit of NF-AT (nuclear factor of activated T cells), repairs DNA breaks, inhibits viral replication, and also functions as a negative regulator in the microRNA processing pathway in combination with NF90. Recently, it was found that implicated in the mitotic control of HeLa cells and deletion of endogenous NF45 decreases growth of HeLa cells. While the role of NF45 in cancer biology remains under debate. In this study, we analyzed the expression and clinical significance of NF45 in esophageal squamous cell carcinoma ESCC. The expression of NF45 was evaluated by Western blot in 8 paired fresh ESCC tissues and immunohistochemistry on 105 paraffin-embedded slices. NF45 was highly expressed in ESCC and significantly associated with ESCC cells tumor stage and Ki-67. Besides, high NF45 expression was an independent prognostic factor for ESCC patients' poor survival. To determine whether NF45 could regulate the proliferation of ESCC cells, we increased endogenous NF45 and analyzed the proliferation of TE1 ESCC cells using Western blot, CCK8, flow cytometry assays and colony formation analyses, which together indicated that overexpression of NF45 favors cell cycle progress of TE1 ESCC cells. While knockdown of NF45 resulted in cell cycle arrest at G0/G1-phase and thus abolished the cell growth. These findings suggested that NF45 might play an important role in promoting the tumorigenesis of ESCC, and thus be a promising therapeutic target to prevent ESCC progression.

背景与目标： ：NF45（也称为ILF2），作为NF-AT（活化的T细胞的核因子）的一个亚基，修复DNA断裂，抑制病毒复制，并与NF90一起在microRNA加工途径中起负调控作用。最近，发现牵涉HeLa细胞的有丝分裂控制和内源性NF45的缺失降低HeLa细胞的生长。尽管NF45在癌症生物学中的作用仍在争论中。在这项研究中，我们分析了NF45在食管鳞状细胞癌ESCC中的表达及其临床意义。通过Western印迹法在8对配对的ESCC组织中对NF45的表达进行了评估，并在105个石蜡包埋的切片上进行了免疫组织化学分析。 NF45在ESCC中高表达，并与ESCC细胞的肿瘤分期和Ki-67显着相关。此外，NF45高表达是ESCC患者生存不良的独立预后因素。为了确定NF45是否能调节ESCC细胞的增殖，我们增加了内源性NF45并使用Western blot，CCK8，流式细胞术和集落形成分析来分析TE1 ESCC细胞的增殖，这共同表明NF45的过表达有利于NF45的细胞周期进程。 TE1 ESCC细胞。而敲低NF45导致细胞周期停滞在G0 / G1期，从而废除了细胞生长。这些发现表明NF45可能在促进ESCC的肿瘤发生中起重要作用，因此是预防ESCC进展的有希望的治疗靶标。

BACKGROUND & AIMS: OBJECTIVE:To determine whether the combination of prostaglandin E2 (PGE2) and EP2, the subtype receptor of PGE2, could trans-activate the epidermal growth factor receptor (EGFR). PATIENTS AND METHODS:In this experiment, we selected epithelial cells from normal esophageal mucosa as the negative control group, and the ESCC EC109 and TE-1 cell strain as the observation group. Real-time PCR and Western-blotting were used to detect the expression of EP2, EGFR and phosphorylated EGFR (p-EGFR). The pre-treatment of ESCC cell strains was carried out using Butaprost (special agonist of PGE2 and EP2) and RNAi of EP2, and we observed the expression of EP2, EGFR, and p-EGFR. WST-8 (CCK-8) was applied for the detection of the cell proliferation rate. The transwell invasion experiment was conducted for the detection of the invasion capability of cells. The expression of MMP-9 (matrix metalloproteinase-9), VEGF (vascular endothelial growth factor), pro-inflammatory factors (IL-6 and TNF-α) in the cell supernatant were detected using ELISA. RESULTS:The high mRNA and protein expression of EP2, EGFR, and p-EGFR were found in the EC109 and TE-1 cell strains in the observation group, which were higher than those in the control group (p < 0.05). After the intervention of PGE2, EP2 expression was decreased and the p-EGFR expression was increased (p < 0.05). There was no variation found in the expression of EGFR (p > 0.05). After cells were intervened using Butaprost, the expressions of EP2 and p-EGFR were increased (p < 0.05), and there were no changes identified in the expression of EGFR (p > 0.05). After the intervention of RNAi, the expression of EP2 and p-EGFR was decreased (p < .05), and no changes were identified in the expression of EGFR (p > 0.05). After the intervention of PGE2 and Butaprost, great increases were seen in the cell proliferation rate, invasion capability, and the expression of MMP-9, VEGF, IL-6, and TNF-α in EC109 and TE-1 cell strains (p < 0.05), however, the intervention of RNAi could reduce above indexes (p < 0.05). CONCLUSIONS:Through cell experiments, we verified that the combination of prostaglandin E2 (PGE2) and EP2, the subtype receptor of PGE2, could trans-activate the epidermal growth factor receptor (EGFR) to regulate the proliferation and invasion capability of esophageal squamous cell carcinoma (ESCC) cells, and secrete and express multiple cytokines, thus discovering the pathological mechanism of inflammation to carcinoma transition in the occurrence of ESCC, and providing the experimental evidence for the search of new target in the treatment of ESCC. ESCC cells can highly express the receptor subtype EP2 of PGE2 that can transactivate the EGFR, through which PGE2 is involved in the transition mechanism from inflammation to cancer.

背景与目标： 目的：确定前列腺素E2（PGE2）和EP2（PGE2的亚型受体）的组合是否可以反激活表皮生长因子受体（EGFR）。
病人与方法：本实验以正常食管粘膜上皮细胞为阴性对照组，以ESCC EC109和TE-1细胞株为观察组。实时PCR和Western-blotting用于检测EP2，EGFR和磷酸化EGFR（p-EGFR）的表达。使用Butaprost（PGE2和EP2的特殊激动剂）和EP2的RNAi进行ESCC细胞株的预处理，我们观察到EP2，EGFR和p-EGFR的表达。 WST-8（CCK-8）用于检测细胞增殖率。进行transwell侵袭实验以检测细胞的侵袭能力。使用ELISA检测细胞上清液中MMP-9（基质金属蛋白酶-9），VEGF（血管内皮生长因子），促炎因子（IL-6和TNF-α）的表达。
结果：观察组EC109和TE-1细胞株中EP2，EGFR和p-EGFR的mRNA和蛋白表达较高，高于对照组（p <0.05）。在PGE2干预后，EP2表达降低，而p-EGFR表达升高（p <0.05）。在EGFR的表达中没有发现变化（p＞ 0.05）。用Butaprost干预细胞后，EP2和p-EGFR的表达增加（p <0.05），而EGFR的表达没有变化（p> 0.05）。 RNAi干预后，EP2和p-EGFR的表达降低（p <.05），而EGFR的表达未见变化（p> 0.05）。在PGE2和Butaprost的干预下，EC109和TE-1细胞株的细胞增殖速率，侵袭能力以及MMP-9，VEGF，IL-6和TNF-α的表达均显着增加（p < 0.05），但是，RNAi的干预可以降低上述指标（p <0.05）。
结论：通过细胞实验，我们证实前列腺素E2（PGE2）和EP2（PGE2的亚型受体）的组合可以反激活表皮生长因子受体（EGFR）来调节食管鳞状细胞癌的增殖和侵袭能力。 （ESCC）细胞，并分泌和表达多种细胞因子，从而发现了发生ESCC时炎症向癌变的病理机制，为寻找ESCC的新靶标提供了实验依据。 ESCC细胞可以高表达PGE2的受体亚型EP2，该亚型可以使EGFR活化，PGE2可以通过该亚型参与从炎症到癌症的转变机制。

BACKGROUND & AIMS: Background:Radiotherapy is one of the most important treatments for esophageal squamous cell carcinoma (ESCC). Previously, we found that EphA5 expression was increased in ESCC cells and tumor tissues. Studies from other groups reported that EphA5 is abnormally expressed in numerous malignant tumors and may be involved in the radiosensitivity of lung cancer. However, the role of EphA5 in radiotherapy for ESCC remains unclear. Methods:The siRNA sequences against human EPHA5 were transfected to the ESCC cells (KYSE150 and KYSE450). After ionizing radiation (IR), cell viability and colony formation assays were used to test the changes of cell proliferation in EphA5-silenced cells. Flow cytometry analysis was performed to investigate the cell apoptosis and cycle in the irradiated cells interfered by siRNA. The key molecules involved in cell cycle checkpoints and DNA damage repair were evaluated by Western blot and immunofluorescence. Results:CCK8 assay and clonogenic assay showed that the proliferation of EphA5-silenced ESCC cells was inhibited after IR. At 24 h post-IR treatment, we found that the G1/S checkpoint triggered by DNA damage in EphA5-silenced cells was defective. γ-H2AX foci in the irradiated EphA5-silenced cells were impaired at 0.5 h post-IR treatment as well as ATM activation. The defective activation of ATM resulted in a decrease of p-Chk2, p-p53 and p21 expression. Conclusion:In conclusion, these results indicate that EphA5 silencing increases radiosensitivity in ESCC cells through ATM-dependent pathway, which provides a potential target for the radiotherapy in ESCC.

背景与目标： 背景：放射治疗是食管鳞状细胞癌（ESCC）的最重要治疗方法之一。以前，我们发现EphA5表达在ESCC细胞和肿瘤组织中增加。其他研究表明，EphA5在许多恶性肿瘤中异常表达，可能与肺癌的放射敏感性有关。然而，EphA5在ESCC放射治疗中的作用尚不清楚。
方法：将针对人类EPHA5的siRNA序列转染至ESCC细胞（KYSE150和KYSE450）。电离辐射（IR）后，细胞活力和集落形成测定法用于测试EphA5沉默的细胞中细胞增殖的变化。进行流式细胞术分析以研究被siRNA干扰的被照射细胞的细胞凋亡和周期。通过蛋白质印迹和免疫荧光评估了参与细胞周期检查点和DNA损伤修复的关键分子。
结果：CCK8法和克隆形成法显示，IR后，EphA5沉默的ESCC细胞的增殖受到抑制。红外线治疗后24小时，我们发现由EphA5沉默的细胞中的DNA损伤触发的G1 / S检查点存在缺陷。照射后的EphA5沉默的细胞中的γ-H2AX焦点在IR处理以及ATM激活后0.5小时受到损害。 ATM激活缺陷导致p-Chk2，p-p53和p21表达降低。
结论：总之，这些结果表明，EphA5沉默可通过ATM依赖性途径提高ESCC细胞的放射敏感性，这为ESCC放射治疗提供了潜在的靶标。

BACKGROUND & AIMS: :Tumor associated macrophages (TAMs) play an important role in the growth, progression, and metastasis of tumors. The distribution of TAMs in Kazakh esophageal squamous cell carcinoma (ESCC) is not determined. We aimed to investigate the role of TAMs in the occurrence and progression of Kazakh ESCC. CD163 was used as the TAM marker, and immunohistochemistry (IHC) counts were used to quantify the density of TAMs in tumor nest and surrounding stroma. IHC staining was used to evaluate the expression of vascular endothelial growth factor C (VEGF-C) in Kazakh ESCC and cancer adjacent normal (CAN) tissues. The density of TAMs in Kazakh ESCCs tumor nest and stromal was significantly higher than that in CAN tissues. The increased number of CD163-positive TAMs in tumor nest and tumor stromal was positively associated with Kazakh ESCC lymph node metastasis and clinical stage progression. Meanwhile, the expression of VEGF-C in Kazakh ESCCs was significantly higher than that in CAN tissues. Overexpression of VEGF-C in Kazakh ESCCs was significantly associated with gender, depth of tumor invasion, lymph node metastasis and tumor clinical stage. The increased number of TAMs, either in the tumor nests or tumor stroma was positively correlated with the overexpression of VEGF-C, which may promote lymphangiogenesis and play an important role in the invasion and metastasis of Kazakh ESCC.

背景与目标： ：肿瘤相关的巨噬细胞（TAM）在肿瘤的生长，进展和转移中起重要作用。在哈萨克人食管鳞状细胞癌（ESCC）中TAM的分布尚未确定。我们旨在调查TAM在哈萨克ESCC发生和发展中的作用。 CD163用作TAM标记，免疫组化（IHC）计数用于量化肿瘤巢和周围基质中TAM的密度。 IHC染色用于评估哈萨克斯坦ESCC和癌旁正常组织（CAN）中血管内皮生长因子C（VEGF-C）的表达。哈萨克ESCCs肿瘤巢和基质中TAMs的密度显着高于CAN组织中的TAMs的密度。肿瘤巢和肿瘤基质中CD163阳性TAM数量的增加与哈萨克斯坦ESCC淋巴结转移和临床分期进展呈正相关。同时，哈萨克人食管鳞癌中VEGF-C的表达明显高于CAN组织。哈萨克人食管鳞癌中VEGF-C的过度表达与性别，肿瘤浸润深度，淋巴结转移和肿瘤临床分期显着相关。无论是在肿瘤巢中还是在肿瘤基质中，TAM的数量增加都与VEGF-C的过表达呈正相关，这可能促进淋巴管生成，并在哈萨克ESCC的侵袭和转移中起重要作用。

BACKGROUND & AIMS: :Esophageal squamous cell carcinoma (ESCC) is one of the most malignant gastrointestinal cancers and occurs at a high frequency rate in China and other Asian countries. Recently, several molecular markers were identified for predicting ESCC. Notwithstanding, additional prognostic markers, with a clear understanding of their underlying roles, are still required. Through bioinformatics, a graph-clustering method by DPClus was used to detect co-expressed modules. The aim was to identify a set of discriminating genes that could be used for predicting ESCC through graph-clustering and GO-term analysis. The results showed that CXCL12, CYP2C9, TGM3, MAL, S100A9, EMP-1 and SPRR3 were highly associated with ESCC development. In our study, all their predicted roles were in line with previous reports, whereby the assumption that a combination of meta-analysis, graph-clustering and GO-term analysis is effective for both identifying differentially expressed genes, and reflecting on their functions in ESCC.

背景与目标： 食管鳞状细胞癌（ESCC）是最恶性的胃肠道癌之一，在中国和其他亚洲国家以很高的频率发生。最近，鉴定了几种分子标志物来预测ESCC。尽管如此，仍然需要其他的预后指标，并清楚地了解其潜在作用。通过生物信息学，使用DPClus的图聚类方法检测共表达的模块。目的是确定一组可用于通过图聚类和GO项分析预测ESCC的区分基因。结果表明，CXCL12，CYP2C9，TGM3，MAL，S100A9，EMP-1和SPRR3与ESCC的发展高度相关。在我们的研究中，它们的所有预测作用均与以前的报告一致，因此，假设荟萃分析，图聚类和GO项分析相结合可有效识别差异表达的基因并反映其在ESCC中的功能。

BACKGROUND & AIMS: :CtBP2, as a transcriptional corepressor of epithelial-specific genes, has been reported to promote tumor due to upregulating epithelial-mesenchymal transition (EMT) in cancer cells. CtBP2 was also demonstrated to contribute to the proliferation of esophageal squamous cell carcinoma (ESCC) cells through a negative transcriptional regulation of p16(INK4A). In this study, for the first time, we reported that CtBP2 expression, along with CCNH/CDK7, was higher in ESCC tissues with lymph node metastases than in those without lymph node metastases. Moreover, both CtBP2 and CCNH/CDK7 were positively correlated with E-cadherin, tumor grade, and tumor metastasis. However, the concrete mechanism of CtBP2's role in enhancing ESCC migration remains incompletely understood. We confirmed that CCNH/CDK7 could directly interact with CtBP2 in ESCC cells in vivo and in vitro. Furthermore, our data demonstrate for the first time that CtBP2 enhanced the migration of ESCC cells in a CCNH/CDK7-dependent manner. Our results indicated that CCNH/CDK7-CtBP2 axis may augment ESCC cell migration, and targeting the interaction of both may provide a novel therapeutic target of ESCC.

背景与目标： ：CtBP2，作为上皮特异性基因的转录共抑制子，由于在癌细胞中上皮-间质转化（EMT）上调而促进了肿瘤。还证明了CtBP2通过对p16（INK4A）的负转录调节来促进食管鳞状细胞癌（ESCC）细胞的增殖。在本研究中，我们首次报道，在有淋巴结转移的ESCC组织中，CtBP2表达以及CCNH / CDK7高于无淋巴结转移的ESCC组织。此外，CtBP2和CCNH / CDK7与E-钙粘蛋白，肿瘤等级和肿瘤转移均呈正相关。但是，对CtBP2在增强ESCC迁移中作用的具体机制尚不完全了解。我们证实，CCNH / CDK7可以在体内和体外直接与ESCC细胞中的CtBP2相互作用。此外，我们的数据首次证明CtBP2以CCNH / CDK7依赖性方式增强了ESCC细胞的迁移。我们的研究结果表明CCNH / CDK7-CtBP2轴可能会增加ESCC细胞的迁移，并且靶向两者的相互作用可能会提供ESCC的新型治疗靶点。

BACKGROUND & AIMS: :The purpose of this study was to explore the relationship between the expression of vascular endothelial growth factor (VEGF), human epidermal growth factor receptor 2 (HER-2), and epidermal growth factor receptor (EGFR) mRNA in esophageal squamous cell carcinoma (ESCC) and the clinicopathological characteristics of the Han, Uyghur, and Kazakh in Xinjiang. Real-time quantitative polymerase chain reaction technology (RT-PCR) was used to detect the expression of VEGF, HER-2, and EGFR mRNA in esophageal squamous cancer tissue of 60 cases and 30 cases of VEGF, HER-2, and EGFR mRNA in esophageal cancer adjacent tissues, and analyze its relationship with clinicopathological features. The results were as follows: (1) There was no statistically significant difference in esophageal tissue VEGF, HER-2, and EGFR mRNA gene expression levels of the Han, Uyghur, and Kazakh patients (P > 0.05). (2) The expression levels of VEGF, HER-2, and EGFR mRNA in ESCC group were higher than those in adjacent esophageal tissue group (P < 0.05). (3) The expression levels of VEGF and HER-2 mRNA in ESCC of the Han patients were higher than those of the Uyghur and Kazakh patients (P < 0.05). (4) The expression levels of VEGF, HER-2, and EGFR mRNA in lymph node metastases were higher than those without lymph node metastasis (P < 0.05). (5) The expression level of HER-2 mRNA was related with the degrees of pathological differentiation, and the higher pathologic degree, the lower expression level in HER-2 mRNA (P < 0.05). Therefore, the following conclusions were drawn: (1) There were ethnic differences in the VEGF and HER-2 gene mRNA expression levels of the Uyghur, Han, and Kazakh patients in Xinjiang. (2) The expressions of VEGF, HER-2, and EGFR mRNA were related to the lymph node metastasis in ESCC and pathologic differentiation degree.

背景与目标： ：本研究旨在探讨食管鳞状细胞癌中血管内皮生长因子（VEGF），人表皮生长因子受体2（HER-2）和表皮生长因子受体（EGFR）mRNA的表达之间的关系（ ESCC）和新疆汉族，维吾尔族和哈萨克族的临床病理特征。采用实时定量聚合酶链反应技术（RT-PCR）检测60例食管鳞癌组织和30例VEGF，HER-2和EGFR mRNA的食管鳞癌组织中VEGF，HER-2和EGFR mRNA的表达。在食管癌附近组织中，并分析其与临床病理特征的关系。结果如下：（1）汉族，维吾尔族和哈萨克族患者食管组织VEGF，HER-2和EGFR mRNA基因表达水平差异无统计学意义（P> 0.05）。 （2）食管鳞癌组VEGF，HER-2和EGFR mRNA的表达水平高于邻近食管组织组（P <0.05）。 （3）汉族人食管鳞癌中VEGF和HER-2 mRNA的表达水平高于维吾尔族和哈萨克族人（P <0.05）。 （4）淋巴结转移中VEGF，HER-2，EGFR mRNA的表达水平高于无淋巴结转移者（P <0.05）。 （5）HER-2 mRNA的表达水平与病理分化程度有关，病理程度越高，HER-2 mRNA的表达水平越低（P <0.05）。因此，得出以下结论：（1）新疆维吾尔族，汉族和哈萨克族患者的VEGF和HER-2基因mRNA表达水平存在种族差异。 （2）VEGF，HER-2，EGFR mRNA的表达与ESCC淋巴结转移及病理分化程度有关。

BACKGROUND & AIMS: BACKGROUND:Esophageal squamous cell carcinoma (ESCC) is one of the most lethal malignancies. Latest studies report that long noncoding RNAs (LncRNAs) play an essential role in diversified pathological processes of ESCC, although the mechanism by which they do so remains unknown. This study aimed to explore the parts of lncRNA taurine upregulated gene 1 (TUG1) in ESCC tissues and cells, its biofunctional effect and its underlying regulatory mechanism in ESCC. METHODS:The levels of TUG1 and miR-148a-3p were detected by quantitative real-time polymerase chain reaction (qRT-PCR) in ESCC cells and tissues. The biofunctional effects were examined by MTT, flow cytometry, and transwell assay. The protein expression levels of epithelial-mesenchymal transition (EMT)-related proteins and MCL-1 were determined by western blot analysis. The binding sites between miR-148a-3p and TUG1 or MCL-1 were predicted by online software starBase and confirmed by dual luciferase reporter assay. RESULTS:The mRNA expression of TUG1 was significantly upregulated in ESCC tissues or cells, and was negatively correlated to miR-148a-3p expression in tissues. Knockdown of TUG1 inhibited the proliferation, migration, and invasion, promoted apoptosis, and relieved the EMT progression in EC9706 and OE19 cells. Besides, knockdown of miR-148a-3p inverted positive effects from TUG1 deletion on ESCC cells. Besides, MCL-1 reversed the inhibitive effects from TUG1 deletion on expression of EMT-associated proteins (Wnt1, C-myc, CyclinD1, and β-catenin) above subsequently. CONCLUSION:TUG1 regulated the biofunction and EMT progression of ESCC by mediating miR-148a-3p/MCL-1/Wnt/β-catenin axis in vitro.

背景与目标： 背景：食管鳞状细胞癌（ESCC）是最致命的恶性肿瘤之一。最新研究报道，长的非编码RNA（LncRNA）在ESCC的多种病理过程中起着至关重要的作用，尽管其作用机理尚不清楚。这项研究旨在探讨ESCC组织和细胞中lncRNA牛磺酸上调基因1（TUG1）的部分，其生物功能作用及其在ESCC中的潜在调控机制。
方法：采用定量实时聚合酶链反应（qRT-PCR）检测ESCC细胞和组织中TUG1和miR-148a-3p的水平。通过MTT，流式细胞术和transwell测定法检查生物功能作用。通过蛋白质印迹分析确定上皮-间质转化（EMT）相关蛋白和MCL-1的蛋白表达水平。通过在线软件starBase预测了miR-148a-3p与TUG1或MCL-1之间的结合位点，并通过双重荧光素酶报告基因测定法进行了确认。
结果：在食管鳞癌组织或细胞中TUG1的mRNA表达明显上调，与组织中miR-148a-3p的表达呈负相关。敲低TUG1抑制EC9706和OE19细胞的增殖，迁移和侵袭，促进细胞凋亡，并缓解EMT进展。此外，敲除miR-148a-3p可以逆转TUG1缺失对ESCC细胞的积极作用。此外，MCL-1随后逆转了TUG1缺失对上述EMT相关蛋白（Wnt1，C-myc，CyclinD1和β-catenin）表达的抑制作用。
结论：TUG1通过介导miR-148a-3p / MCL-1 / Wnt /β-catenin轴调控ESCC的生物学功能和EMT进程。

BACKGROUND & AIMS: :The paucity of new drugs for the treatment of esophageal squamous cell carcinoma (ESCC) limits the treatment options. This study characterized the therapeutic efficacy and action mechanism of a novel natural macrolide compound F806 in human ESCC xenograft models and cell lines. F806 inhibited growth of ESCC, most importantly, it displayed fewer undesirable side effects on normal tissues in two human ESCC xenograft models. F806 inhibited proliferation of six ESCC cells lines, with the half maximal inhibitory concentration (IC50) ranging from 9.31 to 16.43 μM. Furthermore, F806 induced apoptosis of ESCC cells, contributing to its growth-inhibitory effect. Also, F806 inhibited cell adhesion resulting in anoikis. Mechanistic studies revealed that F806 inhibited the activation of β1 integrin in part by binding to a novel site Arg610 of β1 integrin, suppressed focal adhesion formation, decreased cell adhesion to extracellular matrix and eventually triggered apoptosis. We concluded that F806 would potentially be a well-tolerated anticancer drug by targeting β1 integrin, resulting in anoikis in ESCC cells.

背景与目标： ：食管鳞状细胞癌（ESCC）的新药匮乏，限制了治疗方案的选择。这项研究的特点是新型的天然大环内酯化合物F806在人类ESCC异种移植模型和细胞系中的治疗功效和作用机理。 F806抑制了ESCC的生长，最重要的是，它在两种人类ESCC异种移植模型中对正常组织的不良副作用更少。 F806抑制了6种ESCC细胞系的增殖，最大抑制浓度（IC50）的一半在9.31至16.43μM之间。此外，F806诱导ESCC细胞凋亡，有助于其生长抑制作用。同样，F806抑制细胞粘附，导致阳极失调。机理研究表明，F806部分通过与β1整合素的新位点Arg610结合而抑制β1整合素的活化，抑制了粘着斑的形成，减少了细胞对细胞外基质的粘附，并最终触发了细胞凋亡。我们得出的结论是，通过靶向β1整联蛋白，F806可能是一种耐受良好的抗癌药物，从而导致ESCC细胞失衡。

BACKGROUND & AIMS: :Accumulating evidences demonstrate that a population of suppressive cells known as myeloid-derived suppressor cells (MDSCs) is key immune modulators which suppress antitumor immunity. In this study, we found that the level of circulating CD14(+)HLA-DR(-/low) cells in patients was significantly higher than that of healthy donors and was correlated with tumor burden, lymph node metastasis, and tumor, node, and metastasis (TNM) clinical stage. More importantly, we for the first time find the level of CD14(+)HLA-DR(-/low) is a biological indicator of poor prognosis through the analysis of 3-year overall survival. Furthermore, we evidenced that the proportion of CD14(+)HLA-DR(-/low) cells in the tumor metastatic tumor-draining lymph nodes (TDLNs) was notably higher compared to tumor-free TDLNs. Additionally, CD14(+)HLA-DR(-/low) cells from esophageal squamous cell carcinoma (ESCC) patients expressed dramatically increased programmed death ligand 1 (PD-L1) comparing to that from healthy control. Subsequently, blocking PD-L1 pathway by antibody could effectively reverse the suppressive effect on autologous T cell proliferation mediated by CD14(+)HLA-DR(-/low) cells in vitro. In conclusion, our data revealed CD14(+)HLA-DR(-/low) MDSCs which increase in ESCC patients is a novel poor prognostic indicator and may exert immunosuppressive properties through PD-L1/PD-1 pathway.

背景与目标： ：越来越多的证据表明，称为髓样抑制细胞（MDSC）的抑制细胞群是抑制抗肿瘤免疫力的关键免疫调节剂。在这项研究中，我们发现患者中循环CD14（）HLA-DR（-/ low）细胞的水平显着高于健康供体，并且与肿瘤负荷，淋巴结转移以及肿瘤，淋巴结转移有关。转移（TNM）临床阶段。更重要的是，通过3年总生存期的分析，我们首次发现CD14（）HLA-DR（-/低）的水平是预后不良的生物学指标。此外，我们证明在肿瘤转移性肿瘤引流淋巴结（TDLNs）中的CD14（）HLA-DR（-/ low）细胞所占的比例明显高于无肿瘤的TDLNs。此外，与健康对照组相比，食管鳞癌（ESCC）患者的CD14（）HLA-DR（-/ low）细胞表达的程序性死亡配体1（PD-L1）显着增加。随后，通过抗体阻断PD-L1途径可有效逆转体外对CD14（）HLA-DR（-/ low）细胞介导的自体T细胞增殖的抑制作用。总之，我们的数据显示，在ESCC患者中CD14（）HLA-DR（-/低）MDSCs增加是一种新的不良预后指标，并且可能通过PD-L1 / PD-1途径发挥免疫抑制作用。