The possible molecular mechanism underlying the involvement of the variable shear factor QKI in the epithelial-mesenchymal transformation of oesophageal cancer

Yishuang Cui; Yanan Wu; Yingze Zhu; Wei Liu; Lanxiang Huang; Ziqian Hong; Mengshi Zhang; Xuan Zheng; Guogui Sun

doi:10.1371/journal.pone.0288403

The possible molecular mechanism underlying the involvement of the variable shear factor QKI in the epithelial-mesenchymal transformation of oesophageal cancer

PLoS One. 2023 Jul 10;18(7):e0288403. doi: 10.1371/journal.pone.0288403. eCollection 2023.

Authors

Yishuang Cui^{1

2}, Yanan Wu^{1

2}, Yingze Zhu^{2

3

4}, Wei Liu^{2

3

4}, Lanxiang Huang^{2

3

4}, Ziqian Hong^{1

2}, Mengshi Zhang^{1

2}, Xuan Zheng^{1

2}, Guogui Sun^{1

2

3

4}

Affiliations

¹ School of Public Health, North China University of Science and Technology, Tangshan, Hebei Province, China.
² Department of Hebei Key Laboratory of Medical-Industrial Integration Precision Medicine, Tangshan, Hebei Province, China.
³ School of Clinical Medicine, North China University of Science and Technology, Tangshan, Hebei Province, China.
⁴ Affiliated Hospital, North China University of Science and Technology, Tangshan, Hebei Province, China.

Abstract

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.

Copyright: © 2023 Cui et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Epithelial-Mesenchymal Transition / genetics
Esophageal Neoplasms* / genetics
Humans
Matrix Metalloproteinase 1 / metabolism
Matrix Metalloproteinase 10 / metabolism
MicroRNAs* / genetics
RNA, Circular / genetics
RNA, Messenger / metabolism
RNA-Binding Proteins

Substances

RNA, Circular
Matrix Metalloproteinase 1
Matrix Metalloproteinase 10
MicroRNAs
RNA, Messenger
QKI protein, human
RNA-Binding Proteins

Grants and funding

General Project of National Natural Science Foundation of China (82172658); Tangshan small cell lung cancer medical-industrial integration precision diagnosis and treatment basic innovation team (21130203D). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.