MiR-4739 inhibits the malignant behavior of esophageal squamous cell carcinoma cells via the homeobox C10/vascular endothelial growth factor A/phosphatidylinositol 3-kinase/AKT pathway

Abstract

Esophageal cancer is a lethal disease, and emerging evidence has shown that microRNAs are involved in its development, progression, and clinical outcome. MicroRNAs are potential biomarkers for esophageal squamous cell carcinoma (ESCC), and may be useful in advanced RNA therapy for ESCC. This study was conducted to evaluate the molecular mechanism of miR-4739 in ESCC. Reverse transcription-quantitative polymerase chain reaction and western blotting were performed to measure RNA and protein levels. Transwell assay, Cell Counting Kit-8 assay, cytometry analysis, and human umbilical vein endothelial cell tube formation assay were conducted to determine the molecular function of miR-4739 in ESCC. Potential targets of miR-4739 were predicted using bioinformatics tools and confirmed in ESCC cells using a luciferase reporter and RNA pulldown assay. Finally, we performed immunohistochemistry to evaluate the effects of administering agomir-4739 to a mouse model of ESCC. MiR-4739 expression was downregulated in ESCC tissues and cells. MiR-4739 overexpression inhibited cell proliferation, migration, and invasion, and promoted apoptosis of ESCC cells. Furthermore, vascular endothelial growth factor A expression was downregulated by miR-4739 mimics in ESCC cells. MiR-4739 negatively regulated homeobox C10 expression. Additionally, agomir-4739 inhibited tumor growth and angiogenesis in vivo . We demonstrated that miR-4739 overexpression exerted an inhibitory effect on ESCC cells by preventing the expression of homeobox C10 via the vascular endothelial growth factor A/phosphatidylinositol 3-kinase/AKT pathway, indicating the potential of this microRNA as a treatment target in ESCC.

Role of microRNA-4739 in enhancing cisplatin chemosensitivity by negative regulation of RHBDD2 in human cervical cancer cells

“…Additionally, in gastric cancer, miR-4739 has been found to play a negative role in TYMSOS, thereby suppressing cell proliferation, migration, and invasion [ 27 ]. Furthermore, in the case of ESCC, the overexpression of miR-4739 has shown remarkable potential in inhibiting cell proliferation, migration, and invasion, while concurrently promoting apoptosis [ 17 ]. Collectively, these findings provide further evidence of the tumor-suppressive role of miR-4739 across multiple cancer types.…”

“…Recent research has indicated that miR-4739 is downregulated in gastric cancer [ 13 ], prostate cancer [ 14 ], and lung adenocarcinoma [ 15 ], while it is upregulated in hepatocellular carcinoma [ 16 ]. In terms of functionality, increased expression of miR-4739 has been observed to inhibit the growth of esophageal squamous cell carcinoma (ESCC) cells by suppressing the expression of homeobox C10 [ 17 ]. Nevertheless, there is a lack of information regarding the function and molecular mechanism of miR-4739 in relation to chemoresistance in CC cells.…”