miR­210­3p regulates cell growth and affects cisplatin sensitivity in human ovarian cancer cells via targeting E2F3.

The potential role of microRNA (miR)­210­3p in carcinogenesis and the cisplatin sensitivity of ovarian cancer were evaluated in the present study. The relative expression levels of miR­210­3p in cisplatin­sensitive SKOV­3 cells and cisplatin­resistant SKOV­3/DDP cells were determined using reverse transcription­quantitative polymerase chain reaction analysis. miR­210­3p mimics and inhibitors were transfected into SKOV­3/DDP cells. Cell Counting Kit­8, scratch and Transwell invasion assays and flow cytometry were conducted to evaluate the role of miR­210­3p in ovarian cancer cells. A luciferase reporter assay was used to verify the association between miR­210­3p and E2F transcription factor 3 (E2F3). Drug sensitivity was evaluated by treating the cells with cisplatin. The expression level of miR­210­3p was lower in SKOV­3/DDP cells than in SKOV­3 cells. Compared with the untransfected control, SKOV­3 cells transfected with miR­210­3p exhibited a significantly higher survival rate. The overexpression of miR­210­3p inhibited SKOV­3/DDP cell proliferation, migration and invasion, and promoted cell apoptosis. By contrast, the inhibition of miR­210­3p promoted cell migration and invasion. The luciferase reporter assay confirmed that E2F3 was a direct target gene of miR­210­3p. Cisplatin treatment resulted in a sharp decrease in the survival rate of SKOV­3/DDP cells transfected with the miR­210­3p mimics. The decrease in cell survival rate caused by the overexpression of miR­210­3p was rescued by the overexpression of E2F3 in SKOV­3/DDP cells. Taken together, these results suggest that miR­210­3p may act as a tumor suppressor in ovarian cancer cells and affect the sensitivity of cells to cisplatin by directly targeting E2F3. This indicates its potential use as a therapeutic target for improving drug resistance in ovarian cancer.

MiR-203 sensitizes glioma cells to temozolomide and inhibits glioma cell invasion by targeting E2F3.

Glioma is the most common malignant and fatal primary tumor in the central nervous system in adults. Recent data has suggested a profound role for microRNAs (miRs) in cancer progression. The present study demonstrated, via quantitative polymerase chain reaction (qPCR) analysis, that miR-203 expression was markedly lower in highly invasive U87MG glioma cells and glioma tissues. Wound healing and Transwell assays demonstrated that restoration of miR-203 expression inhibited U87MG cell migration and invasion. Restoration of miR-203 expression additionally sensitized the cells to temozolomide (TMZ) as determined by MTS assay. By contrast, miR-203 inhibition in A172 cells exerted opposite effects. Bioinformatic analysis combined with experimental analysis revealed that miR-203 directly targeted E2F3 via the conserved miR-203 target site within the E2F3 3'-untranslational region. E2F3 knockdown with specific small hairpin RNA also inhibited U87MG cell migration and invasion, and sensitized them to TMZ. Importantly, miR-203 and E2F3 showed inverse expression patterns in invasive glioma tissues, as demonstrated by qPCR and luciferase assay. These results suggested that miR-203 may function as a tumor suppressor in glioma progression and that the miR-203/E2F3 axis may be a novel candidate in the development of rational therapeutic strategies for glioma.

miR-141 suppresses the growth and metastasis of HCC cells by targeting E2F3.

MicroRNAs (miRNAs) function as essential post-transcriptional modulators of gene expression involved in a wide range of physiologic and pathologic states, including cancer. Numerous miRNAs have been deregulated in hepatocellular carcinoma (HCC). Here, we investigated the role of miR-141 in HCC. Decreased expression of miR-141 was observed in both HCC tissues and cell lines. Ectopic overexpression of miR-141 reduced proliferation, migration, and invasion of HCC cells. E2F transcription factor 3 (E2F3) was confirmed to be a target of miR-141 in HCC cells. Moreover, restoration of E2F3 significantly reversed the tumor suppressive effects of miR-141. Our results suggest a critical role of miR-141 in suppressing metastasis of HCC cells by targeting E2F3.

Exploration of potential ligands against cancer-causing transcription factor E2F3.

The transcription factor-based therapeutic approaches are the mainstay of current anticancer drug design options to develop highly selective agents with novel modes of action. In this paper, a homology model of DNA-binding domain of transcription factor E2F3 was generated according to X-ray structure of E2F4. As a first step of our proposed project aspired towards exploration of highly selective potential E2F3 ligands, we performed structure-based virtual screening of ZINC 3D chemical database by using Dock Blaster server. Then 31 compounds, selected by filtration step, were docked against the prominent DNA binding site residues of E2F3 model. Two of them have shown a promising interaction with respect to binding poses. The aim is to propose new active ligands against neoplasias characterized by overexpression of E2F3 transcription factor.