Abstract
Background
Esophageal squamous cell carcinoma (ESCC) is one of the most common malignant tumors of the gastrointestinal tract. Circular RNAs (circRNAs) are involved in the pathogenesis of cancer. This study aimed to elucidate the role and molecular mechanism of circ_0008726 in ESCC.
Methods
The expression levels of circ_0008726, microRNA (miR)-206 and homeobox A13 (HOXA13) were detected by quantitative real-time PCR (QRT-PCR). Cell counting kit-8 (CCK-8) and 5-Ethynyl-2’-deoxyuridine (EdU) assays were conducted to detect the proliferative ability of ESCC cells. Apoptosis and invasion of ESCC cells were detected by flow cytometry and transwell assays. Tube formation assay was used to detect the angiogenesis of ESCC cells. The expression of related proteins was detected by western blot analysis. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were performed to confirm the interactions among circ_0008726, miR-206 and HOXA13. Xenograft mice model was established to study the in vivo effect of circ_0008726 knockdown.
Results
Expression of circ_0008726 was up-regulated in ESCC tissues and cells. Knockdown of circ_0008726 repressed proliferation, invasion, angiogenesis, and promoted apoptosis of ESCC cells. Circ_0008726 acted as a sponge for miR-206, and HOXA13 was a target of miR-206. The suppressive effects of circ_0008726 knockdown on cell proliferation, invasion, and angiogenesis were abated by miR-206 down-regulation. Meanwhile, overexpression of HOXA13 partially reversed the suppressive effects of miR-206 enrichment on ESCC cell malignant behaviors. Knockdown of circ_0008726 inhibited ESCC tumor growth in vivo.
Conclusion
In short, circ_0008726 exerted the carcinogenic effects to regulate the proliferation, invasion, angiogenesis and apoptosis of ESCC cells by targeting miR-206/HOXA13 axis.
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Availability of data and materials
The analyzed data sets generated during the present study are available from the corresponding author on reasonable request.
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Conceptualization and methodology: Mingwei Shi and Gong Chen; formal analysis and data curation: Gong Chen and Jiqing Hao; validation and investigation: Tingting Han and Mingwei Shi; writing—original draft preparation and writing—review and editing: Tingting Han, Mingwei Shi and Gong Chen; approval of final manuscript: all the authors.
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The present study was approved by the ethical review committee of The First Affiliated Hospital of Anhui Medical University. Written informed consent was obtained from all enrolled patients.
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Han, T., Shi, M., Chen, G. et al. Circ_0008726 promotes malignant progression of ESCC cells through miR-206/HOXA13 pathway. Gen Thorac Cardiovasc Surg 71, 33–45 (2023). https://doi.org/10.1007/s11748-022-01874-8
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DOI: https://doi.org/10.1007/s11748-022-01874-8