MicroRNA-139 suppresses hepatocellular carcinoma cell proliferation and migration by directly targeting Topoisomerase I.

microRNAs (miRNAs) have been determined to be associated with cancer progression and metastasis. Mir-139 is located on 11q13.4 and exhibits anti-oncogenic and anti-metastatic activity in human cancers. It is downregulated in various malignant tumor types. In the present study, the potential functions and targets of miR-139 in hepatocellular carcinoma (HCC) were explored. Using a combinational analysis of four miRNA target prediction tools and biological experiments, it was determined that Topoisomerase I (TOP1) is a direct target of miR-139 in HCC. Several traditional topoisomerase inhibitors have demonstrated anticancer activity, but their side effects outnumbered their anticancer potential. The present study determined that overexpression of miR-139 significantly inhibits HCC cell proliferation (P<0.05) and migration (P<0.05), which is largely due to TOP1 downregulation. The present study indicated that miR-139 exerts a tumor-suppressive effect during hepatocarcinogenesis via the suppression of expression of TOP1; therefore, miR-139 is a promising target for the treatment of HCC.

[microRNA-139 suppresses proliferation of hepatocellular carcinoma cells by silencing of B cell translocation gene 3].

Objective To determine the role of miR-139 in the development of hepatocellular carcinoma (HCC) and to preliminarily clarify the underlying mechanism. Methods CCK-8 assay was performed to investigate the effect of miR-139 on HCC cell proliferation. Four databases, TargetScan, MiRanda, Clip-seq and miRDB, in combination with literature review, were used to predict the downstream pathways and specifically the potential targets of miR-139. The predicted targets were then verified by Western blot analysis and luciferase reporter assay. Results CCK-8 assay confirmed that miR-139 suppressed the proliferation of HCC cells. By the comparisons between the four databases and the review of literatures, a total of five genes (ICK, BTG3, DCBLD2, EIF4G2 and HNRNPF) were predicted as potential targets of miR-139. Western blot and luciferase reporter assay validated that miR-139 could directly inhibit the expression of BTG3 in HCC cells. Conclusion miR-139 can repress the proliferation of HCC cells via directly inhibiting the expression of BTG3.

Enhancement of X-ray Induced Apoptosis by Mobile Phone-Like Radio-Frequency Electromagnetic Fields in Mouse Spermatocyte-Derived Cells.

To explore the combined effects of environmental radio-frequency (RF) field and X-ray, mouse spermatocyte-derived (GC-1) cells were exposed to 1950 MHz RF field at specific absorption rate (SAR) of 3 W/kg for 24 h combined with or without X-ray irradiation at 6 Gy. After treatment, the cell proliferation level was determined by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) Assay and 5-Bromo-2-deoxy Uridine (BrdU) enzyme linked immunosorbent (ELISA) Assay. The apoptosis level was detected by annexin V flow cytometry assay, transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) Assay and Caspase-3 Activity Assay. It was found that the proliferation and apoptosis level did not change in GC-1 cells after RF exposure alone. However, compared with the X-ray group, the proliferation level significantly decreased and the apoptotic rate significantly increased in the RF+X-ray group. Moreover, a significant decrease in Bcl-2 protein expression and increase in Bax protein expression were observed. The findings suggested that RF exposure at SAR of 3 W/kg did not affect apoptosis and proliferation in GC-1 cells by itself, but that it did enhance the effects of X-ray induced proliferation inhibition and apoptosis, in which B-cell lymphoma-2 (Bcl-2) and Bcl-2 associated X protein (Bax) might be involved.