Abstract
Objective: Esophageal carcinoma (ESCA) is a common malignancy characterized by high morbidity and mortality. Our work managed to dissect the modulatory mechanism of E2F1/miR-29c-3p/COL11A1 in the malignant progression and sensitivity of ESCA cells to sorafenib.
Methods: Via bioinformatics approaches, we identified the target miRNA. Subsequently, CCK-8, cell cycle analysis, and flow cytometry were used to check the biological influences of miR-29c-3p on ESCA cells. TransmiR, mirDIP, miRPathDB, and miRDB databases were used as tools for the prediction of upstream transcription factors and downstream genes of miR-29c-3p. The targeting relationship of genes was detected via RNA immunoprecipitation and chromatin immunoprecipitation, which was further validated by dual-luciferase assay. Finally, in vitro experiments revealed the way E2F1/miR-29c-3p/COL11A1 affected sorafenib’s sensitivity, and in vivo experiments were used to verify the way E2F1 and sorafenib impacted ESCA tumor growth.
Results: miR-29c-3p, downregulated in ESCA, could suppress ESCA cell viability, arrest the cell cycle in the G0/G1 phase, and impel apoptosis. E2F1 was found to be upregulated in ESCA and it could abate the transcriptional activity of miR-29c-3p. COL11A1 was found to be a downstream target of miR-29c-3p to enhance cell viability, induce cell cycle arrest in S phase, and constrain apoptosis. Cellular and animal experiments together demonstrated that E2F1 abated the sorafenib’s sensitivity of ESCA cells via miR-29c-3p/COL11A1.
Conclusion: E2F1 affected the viability, cell cycle, and apoptosis of ESCA cells by modulating miR-29c-3p/COL11A1, and it attenuated the sensitivity of ESCA cells to sorafenib, shedding new light on the treatment of ESCA.
Keywords: Sorafenib, E2F1, miR-29c-3p, COL11A1, Malignant progression, Drug sensitivity.
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