摘要: Objectives: Hypermethylation-induced epigenetic silencing of tumour suppressor genes (TSGs) are frequent events during carcinogenesis. MicroRNA-142 (miR-142) is found to be dysregulated in cancer patients to participate into tumour growth, metastasis and angiogenesis. However, the tumour suppressive role of miR-142 and the status of methylation are not fully understood in hepatocellular carcinoma (HCC). Methods: Hepatocellular carcinoma tissues and corresponding non-neoplastic tissues were collected. The expression and function of miR-142 and TGF-beta in two HCC cell lines were determined. The miRNA-mRNA network of miR-142 was analysed in HCC cell lines. Results: We found that the miR-142 expression was reduced in tumour tissues and two HCC cell lines HepG2 and SMMC7721, which correlated to higher TNM stage, metastasis and differentiation. Moreover, miR-142 was identified to directly target and inhibit transforming growth factor beta (TGF-beta), leading to decreased cell vitality, proliferation, EMT and the ability of pro-angiogenesis in TGF-beta-dependent manner. Interestingly, the status of methylation of miR-142 was analysed and the results found the hypermethylated miR-142 in tumour patients and cell lines. The treatment of methylation inhibitor 5-Aza could restore the expression of miR-142 to suppress the TGF-beta expression, which impaired TGF-beta-induced tumour growth. Conclusion: These findings implicated that miR-142 was a tumour suppressor gene in HCC and often hyermethylated to increase TGF-beta-induced development of hepatocellular carcinoma.

摘要: Objectives: The transfer of melanosomes from melanocytes to neighbouring keratinocytes is critical to protect the skin from the deleterious effects of ultraviolet A (UVA) and ultraviolet B (UVB) irradiation; however, the initial factor(s) that stimulates melanosome transfer remains unclear. In this study, we investigated the induction of retinal-dependent calcium (Ca2+) influx in melanocytes (MCs) by UVA or UVB irradiation and the effect of transient receptor potential cation channel subfamily M member 1 (TRPM1) (melastatin1)-related Ca2+ influx on melanosome transfer. Materials and methods: Primary human epidermal MCs were exposed to physiological doses of UVB or UVA light and loaded with a calcium indicator Fluo-4 dye. The change of intracellular calcium of MCs was monitored using a two-photon confocal fluorescence microscopy. MCs were co-cultured with human epidermal keratinocytes (KCs) in the absence or presence of voriconazole (a TRPM1 blocker) or calcium chelators. MCs were also transfected with TRPM1 siRNA for silencing the expression of TRPM1 gene. The melanosome transfer in the co-cultured cells was quantitatively analysed using flow cytometry and was further confirmed by immunofluorescent double-staining. The protein levels and distributions of TRPM1, OPN3 and OPN5 in MCs were measured by Western blotting or immunofluorescent staining. Results: The retinal-dependent Ca2+ influx of UVA-exposed melanocytes differed greatly from that of UVB-exposed melanocytes in the timing-phase. The protein expression of TRPM1 in mono- and co-cultured MCs was dose-dependently up-regulated by UVA and UVB. TRPM1 siRNA-mediated knockdown and the blockage of TRPM1 channel using a putative antagonist (voriconazole) significantly inhibited melanosome transfer in co-cultures following UVA or UVB exposure. Conclusions: The distinct time-phases of Ca2+ influx in MCs induced by UVA or UVB contribute to the consecutive stimulation of melanosome transfer, thereby providing a potent photoprotection against harmful UV radiation.

摘要: Objective: Interferon-inducible 16 (IFI16) is known to involve in p53-dependent tumour suppression and also the formation of inflammasome, which function, however, remains controversy during carcinogenesis as a pattern recognition receptor for tumour death-derived free DNA. In this study, we investigated the anti-tumour role of IFI16 in hepatocellular carcinoma (HCC). Materials and methods: Hepatocellular carcinoma tissues (n = 20) and corresponding non-neoplastic tissues (n = 20) were collected to determine the expression of IFI16. After the transfection of pcDNA3.1-IFI16 into Huh7 and SMMC7721 cells in vitro, the influence of IFI16 overexpression on cell vitality, colony formation, apoptosis and migration were analysed. The role effect of IFI16 in vivo was further investigated. Results: The expression of IFI16 was significantly decreased in tumour tissues and cell lines. Overexpression of IFI16 induced decrease of cell vitality, colony formation and increased apoptosis with impaired ability of migration. Mechanistically, IFI16 could activate p53 at Ser15 to up-regulate the p21(WAF1/CIP1) level to inhibit tumour growth and migration, which was restored by the p53 inhibitor Pifithrin-alpha (20 mu mol/L). Moreover, IFI16-induced tumour cell death promoted the recruitment of inflammasome complex to enhance tumour inhibition, but the caspase-1 inhibitor Ac-YVAD-CMK (50 mu mol/L) could suppress this process in HCC. The results in vivo indicated that restored expression of IFI16 in tumour cells effectively promote tumour regression, which could be partly abrogated by the inhibition of activation of p53 signals or induced inflammasome. Conclusion: IFI16 is a tumour suppressor in HCC via activation of p53 signals and inflammasome.

摘要: In recent years, increasing evidence has shown the potential role of long non-coding RNAs (lncRNAs) in multiple cancers. Deregulation of lncRNAs was detected being closely associated with many kinds of tumours where they can act as a tumour suppressor or accelerator. LINC00152 was identified as an oncogene involved in many kinds of cancers, such as gastric cancer, hepatocellular carcinoma, colon cancer, gallbladder cancer and renal cell carcinoma. Moreover, inhibition of LINC00152 can suppress proliferation, migration and invasion of the cancer cells. Increasing evidence has showed that LINC00152 may act as a diagnostic and prognostic biomarker for the above-mentioned cancers. In our review, we summarize the recent research progress of the expression and role of LINC00152 in various kinds of cancers.

摘要: Objectives: Mesenchymal stem cell (MSC)-mediated periodontal tissue regeneration is considered to be a promising method for periodontitis treatment. The molecular mechanism of functional regulation by MSCs remains unclear, thus limiting their application. Our previous study discovered that Periostin (POSTN) promoted the migration and osteogenic differentiation of periodontal ligament mesenchymal stem cells (PDLSCs), but it is still unclear whether POSTN is able to restore the regenerative potential of PDLSCs under inflammatory conditions. In this study, we investigated the effect of POSTN on PDLSCs under inflammatory conditions and its mechanism. Materials and methods: PDLSCs were isolated from periodontal ligament tissue. TNF-alpha was used at 10 ng/mL to mimic inflammatory conditions. Lentivirus POSTN shRNA was used to knock down POSTN. Recombinant human POSTN (rhPOSTN) was used to stimulate PDLSCs. A scratch assay was used to analyse cell migration. Alkaline phosphatase (ALP) activity, Alizarin Red staining and expression of osteogenesis-related genes were used to investigate the osteogenic differentiation potential. Western blot analysis was used to detect the mitogen-activated protein kinases (MAPK) and AKT signalling pathways. Results: After a 10 ng/mL TNF-alpha treatment, knockdown of POSTN impeded scratch closure, inhibited ALP activity and mineralization in vitro, and decreased expression of RUNX2, OSX, OPN and OCN in PDLSCs, while 75 ng/mL rhPOSTN significantly accelerated scratch closure, enhanced ALP activity and mineralization in vitro, and increased expression of RUNX2, OSX, OPN and OCN. In addition, knockdown of POSTN inhibited expression of phosphorylated c-Jun N-terminal kinase (p-JNK), while 75 ng/mL rhPOSTN increased expression of p-JNK in PDLSCs with TNF-alpha treatment. Furthermore, inhibition of JNK by its inhibitor SP600125 dramatically blocked POSTN-enhanced scratch closure, ALP activity and mineralization in PDLSCs. Conclusions: Our results revealed that POSTN might promote the migration and osteogenic differentiation potential of PDLSCs via the JNK pathway, providing insight into the mechanism underlying MSC biology under inflammatory conditions and identifying a potential target for improving periodontal tissue regeneration.