Background Esophageal squamous cell carcinoma (ESCC) is a common invasive malignancy worldwide with poor clinical outcomes. Increasing amount of long non-coding RNAs (lncRNAs) have been reported to be involved in cancer development. However, lncRNAs that are functional in ESCC and the underlying molecular mechanisms remain largely unknown. Methods Transcriptomic analysis was performed to identify dysregulated lncRNAs in ESCC tissue samples. The high expression of LINC00680 in ESCC was validated by RT-qPCR, and the oncogenic functions of LINC00680 was investigated by cell proliferation, colony formation, migration and invasion assays in ESCC cells in vitro and xenografts derived from ESCC cells in mice. RNA-seq, competitive endogenous RNA (ceRNA) network analysis, and luciferase reporter assays were carried out to identify LINC00680 target genes and the microRNAs (miRNAs) bound to LINC00680. Antisense oligonucleotides (ASOs) were used for in vivo treatment. Results Transcriptome profiling revealed that a large number of lncRNAs was dysregulated in ESCC tissues. Notably, LINC00680 was highly expressed, and upregulation of LINC00680 was associated with large tumor size, advanced tumor stage, and poor prognosis. Functionally, knockdown of LINC00680 restrained ESCC cell proliferation, colony formation, migration, and invasion in vitro and inhibited tumor growth in vivo. Mechanistically, LINC00680 was found to act as a ceRNA by sponging miR-423-5p to regulate PAK6 (p21-activated kinase 6) expression in ESCC cells. The cell viability and motility inhibition induced by LINC00680 knockdown was significantly reversed upon PAK6 restoration and miR-423-5p inhibition. Furthermore, ASO targeting LINC00680 substantially suppressed ESCC both in vitro and in vivo. Conclusions An oncogenic lncRNA, LINC00680, was identified in ESCC, which functions as a ceRNA by sponging miR-423-5p to promote PAK6 expression and ESCC. LINC00680/miR-423-5p/PAK6 axis may serve as promising diagnostic and prognostic biomarkers and therapeutic targets for ESCC.

Circular RNAs (circRNAs) are a type of endogenous non-coding RNA with multiple binding sites that specifically bind to microRNAs (miRNAs) and serve an important role in cellular regulatory networks. Patients exhibit varying levels of lymphatic metastasis in a clinical setting. The present study investigated the association between circRNAs and lymphatic metastasis in esophageal squamous cell carcinoma (ESCC). The tissue samples were divided into three groups, including early tumor stage associated with advanced nodal stage (T1 group), advanced tumor stage associated with early nodal stage (T2 group) and healthy esophageal epithelial tissues as the control group (C group). Gene chip analysis identified circRNAs, and those with possible regulatory functions were validated by reverse transcription-quantitative polymerase chain reaction analysis (RT-qPCR). circRNAs containing miRNA response element (MRE) sequences were obtained, and circRNA/miRNA prediction software was used to predict miRNAs that may interact with circRNA. A total of 12,275 circRNAs were detected, including 861 with statistically significant differences. A comparison between the T1 and C groups identified 152 upregulated circRNAs and 431 downregulated ones, while a comparison between the T2 and C groups identified 187 upregulated and 481 downregulated circRNAs. A T1/T2 group comparison revealed that four circRNAs were upregulated and seven were downregulated (fold change >1.5; P<0.05). The RT-qPCR data and gene chip analysis consistently identified hsa_circRNA_100873 as differentially expressed among the examined groups. A total of five potential MREs and complementary sequences were selected for hsa_circRNA_100873. The results of the present study indicated that multiple differentially expressed circRNAs are involved in the pathogenesis of ESCC, and that upregulation of hsa_circRNA_100873 may be associated with increased lymphatic metastases in ESCC.

Background: To investigate the expression and significance of c-kit and epithelial-mesenchymal transition (EMT) molecules (E-cadherin, N-cadherin, Twist, Snail) in thymic epithelial tumors (TETs). Methods: The tissue microarray technology and immunohistochemistry MaxVisionTM-use kit were used to detect the expression of c-kit and EMT molecular markers in 150 cases of paraffin sections of TET tissue and analysis the correlation between c-kit and EMT molecules and explore the malignancy and the relationship of clinicopathological parameters between c-kit, EMT molecules and TETs. Results: The expression difference of c-kit and EMT molecular markers (E-cadherin, N-cadherin, Snail, Twist) in TETs subtypes was statistically significant (P<0.01) and their positive expression rate of thymic carcinoma was significantly higher than that in thymoma, and the difference was statistically significant, respectively (P<0.01). There is a negative correlation between the expression of c-kit and E-cadherin as well as a positive correlation between the expression level of c-kit, N-cadherin, Twist, and Snail. Furthermore, E-cadherin was negatively correlated with N-cadherin, Twist, and Snail while N-cadherin expression was positively correlated with Twist, Snail. Conclusions: Five indicators (c-kit, E-cadherin, N-cadherin, Twist, and Snail) may determine the malignancy of TETs, especially for distinguishing thymoma and thymic carcinoma.

Background: As an important member of platinum-based chemotherapeutic drugs, cisplatin is effective and is commonly used in the treatment of esophageal cancer. However, repeated use of cisplatin usually causes severe side-effects on patients. Novel approaches should be explored to increase the sensitivity of cancer cells to cisplatin. Methods: The expression level of miR-183 in esophageal cancer tissues and cell lines was measured by quantitative reverse transcriptase real-time PCR (qRT-PCR). The sensitivity of EC cell lines to cisplatin was evaluated by CCK-8 assay and flow cytometry. Luciferase reporter assay was used to confirm the association between miR-183 and FOXO1. The apoptosis pathway of EC cells was tested by Western blot assay. Results: The expression level of miR-183 was increased in esophageal cancer patients' tumor tissues and esophageal cancer cell lines. However, knockdown of miR-183 was found to enhance the effect of cisplatin on inducing the apoptotic cell death of esophageal cancer cells. In the mechanism research, we proved that FOXO1 was the target of miR-183 in esophageal cancer cells. Inhibition of miR-183 increased the expression of FOXO1 to promote the expression of Bim and Noxa. As Bim and Noxa acted as key pro-apoptotic proteins in mitochondrial apoptosis, inhibition of miR-183 enhanced the cisplatin-induced apoptosis pathway in esophageal cancer. Conclusion: Knockdown of miR-183 enhanced the cisplatin-induced apoptosis in esophageal cancer through an increase of FOXO1 expression.