The targets of has_circ_0006646.

Objective
Based on the GEO, TCGA and GTEx databases, we reveal the possible molecular mechanism of the variable shear factor QKI in epithelial mesenchymal transformation (EMT) of oesophageal cancer.
Methods
Based on the TCGA and GTEx databases, the differential expression of the variable shear factor QKI in oesophageal cancer samples was analysed, and functional enrichment analysis of QKI was performed based on the TCGA-ESCA dataset. The percent-spliced in (PSI) data of oesophageal cancer samples were downloaded from the TCGASpliceSeq database, and the genes and variable splicing types that were significantly related to the expression of the variable splicing factor QKI were screened out. We further identified the significantly upregulated circRNAs and their corresponding coding genes in oesophageal cancer, screened the EMT-related genes that were significantly positively correlated with QKI expression, predicted the circRNA-miRNA binding relationship through the circBank database, predicted the miRNA-mRNA binding relationship through the TargetScan database, and finally obtained the circRNA-miRNA-mRNA network through which QKI promoted the EMT process.
Results
Compared with normal control tissue, QKI expression was significantly upregulated in tumour tissue samples of oesophageal cancer patients. High expression of QKI may promote the EMT process in oesophageal cancer. QKI promotes hsa_circ_0006646 and hsa_circ_0061395 generation by regulating the variable shear of BACH1 and PTK2. In oesophageal cancer, QKI may promote the production of the above two circRNAs by regulating variable splicing, and these circRNAs further competitively bind miRNAs to relieve the targeted inhibition of IL-11, MFAP2, MMP10, and MMP1 and finally promote the EMT process.
Conclusion
Variable shear factor QKI promotes hsa_circ_0006646 and hsa_circ_0061395 generation, and downstream related miRNAs can relieve the targeted inhibition of EMT-related genes (IL11, MFAP2, MMP10, MMP1) and promote the occurrence and development of oesophageal cancer, providing a new theoretical basis for screening prognostic markers of oesophageal cancer patients.

## 研究目的
本研究基于基因表达综合数据库（Gene Expression Omnibus, GEO）、癌症基因组图谱（The Cancer Genome Atlas, TCGA）以及基因型组织表达数据库（Genotype-Tissue Expression, GTEx），揭示可变剪接因子QKI在食管癌上皮间质转化（Epithelial-Mesenchymal Transition, EMT）中潜在的分子调控机制。

## 研究方法
本研究依托TCGA与GTEx数据库，分析可变剪接因子QKI在食管癌样本中的差异表达情况，并基于TCGA-ESCA数据集对QKI开展功能富集分析。从TCGASpliceSeq数据库下载食管癌样本的剪接百分比（percent-spliced in, PSI）数据，筛选出与可变剪接因子QKI表达显著相关的基因及可变剪接类型。本研究进一步鉴定出食管癌中显著上调的环状RNA（circular RNA, circRNA）及其对应的编码基因，筛选出与QKI表达呈显著正相关的EMT相关基因；通过circBank数据库预测circRNA与微小RNA（microRNA, miRNA）的结合关系，通过TargetScan数据库预测miRNA与信使RNA（messenger RNA, mRNA）的结合关系，最终构建得到QKI调控食管癌EMT过程的circRNA-miRNA-mRNA调控网络。

## 研究结果
与正常对照组织相比，食管癌患者肿瘤组织样本中QKI的表达水平显著上调。QKI的高表达可能促进食管癌的EMT进程。QKI可通过调控BACH1与PTK2的可变剪接，促进hsa_circ_0006646与hsa_circ_0061395的生成。在食管癌中，QKI可能通过调控可变剪接促进上述两种环状RNA的产生，这些环状RNA进一步通过竞争性结合miRNA，解除对IL-11、MFAP2、MMP10及MMP1的靶向抑制作用，最终促进EMT进程。

## 研究结论
可变剪接因子QKI可促进hsa_circ_0006646与hsa_circ_0061395的生成，其下游相关miRNA可解除EMT相关基因（IL11、MFAP2、MMP10、MMP1）的靶向抑制作用，进而促进食管癌的发生与发展，为食管癌患者预后标志物的筛选提供了全新的理论依据。