Title:E2F1 Reduces Sorafenib’s Sensitivity of Esophageal Carcinoma Cells via
Modulating the miR-29c-3p/COL11A1 Signaling Axis
Volume: 17
Author(s): Zhifeng Ma, Ting Zhu, Haiyong Wang, Bin Wang, Linhai Fu and Guangmao Yu*
Affiliation:
- Department of Thoracic Surgery, Shaoxing People's Hospital (Shaoxing Hospital,Zhejiang University School of Medicine), Shaoxing City, Zhejiang
Province 312000, China
Keywords:
Sorafenib, E2F1, miR-29c-3p, COL11A1, Malignant progression, Drug sensitivity.
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.
