Effects of Smad4 on the expression of caspase­3 and Bcl­2 in human gingival fibroblasts cultured on 3D PLGA scaffolds induced by compressive force.

Human gingival fibroblasts (HGFs) are the main cells that comprise gingival tissue, where they transfer mechanical signals under physiological and pathological conditions. The exact mechanism underlying gingival tissue reconstruction under compressive forces remains unclear. The present study aimed to explore the effects of Smad4, caspase­3 and Bcl­2 on the proliferation of HGFs induced by compressive force. HGFs were cultured on poly(lactide­co­glycolide) (PLGA) scaffolds under an optimal compressive force of 25 g/cm2. Cell viability was determined via Cell Counting Kit­8 assays at 0, 12, 24, 48 and 72 h. The expression levels of Smad4, caspase­3 and Bcl­2 were measured via reverse transcription­quantitative PCR and western blotting. The application of compressive force on HGFs for 24 h resulted in a significant increase in cell proliferation and Bcl­2 expression, but a significant decrease in the expression of Smad4 and caspase­3; however, inverse trends were observed by 72 h. Subsequently, a lentivirus was used to overexpress Smad4 in HGFs, which attenuated the effects of compressive force on HGF proliferation and Bcl­2 expression, but enhanced caspase­3 expression, suggesting that Smad4 may regulate compressive force­induced apoptosis in HGFs. In conclusion, these findings increased understanding regarding the mechanisms of compressive force­induced HGF proliferation and apoptosis, which may provide further insight for improving the efficacy and stability of orthodontic treatment.

MicroRNA-627-5p inhibits the proliferation of hepatocellular carcinoma cells by targeting BCL3 transcription coactivator.

Hepatocellular carcinoma (HCC) is a common malignant tumour. An increasing number of studies indicate that microRNAs (miRNAs) are critical regulators in the carcinogenesis and progression of HCC. MiR-627-5p has been identified as a tumour suppressor in colorectal cancer and glioblastoma multiforme. However, the function of miR-627-5p in HCC progression remains unclear yet. In our present study, miR-627-5p was determined to be low-expressed in HCC tissues and cell lines. Furthermore, miR-627-5p was expressed at significantly lower levels in HCC tissues with tumour size >5 cm or advanced tumour stages (III+IV). Additionally, HCC patients with low miR-627-5p level had a significantly poorer overall survival. Functionally, ectopic expression of miR-627-5p obviously inhibited the proliferation, and induced G1 phase arrest and apoptosis of Hep3B and SMMC-7721 cells. Conversely, miR-627-5p silencing facilitated HCC cell proliferation, cell cycle progression and apoptosis resistance. In vivo experiments further confirmed that miR-627-5p overexpression repressed the growth of Hep3B cells in mice. Mechanistically, BCL3 transcription coactivator was predicted as a direct target of miR-627-5p. MiR-627-5p overexpression reduced, whereas miR-627-5p knockdown enhanced the expression of BCL3 protein in HCC cells. Luciferase reporter assay confirmed the direct binding between miR-627-5p and 3'UTR of BCL3. The expression of BCL3 protein was negatively correlated with miR-627-5p level in HCC tissues. More importantly, re-expression of BCL3 partially reversed miR-627-5p induced inhibitory effects on Hep3B cells. In conclusion, these results demonstrated that miR-627-5p functioned as a tumour suppressor in HCC possibly by attenuating BCL3. This finding might offer a new therapeutic target for HCC treatment.