Hepatocellular carcinoma (HCC) accounts for approximately 85%-90% of primary liver cancers. Based on in silico analysis, differentially expressed long non-coding RNA (lncRNA) LINC01224 in HCC, the downstream microRNA (miRNA) miR-330-5p, and its target gene checkpoint kinase 1 (CHEK1) were selected as research subjects. Herein, this study was designed to evaluate their interaction effects on the malignant phenotypes of HCC cells. LINC01224 and CHEK1 were upregulated and miR-330-5p was downregulated in HCC cells. miR-330-5p shared negative correlations with LINC01224 and CHEK1, and LINC01224 shared a positive correlation with CHEK1. Notably, LINC01224 could specifically bind to miR-330-5p, and CHEK1 was identified as a target gene of miR-330-5p. When LINC01224 was silenced or miR-330-5p was elevated, the sphere and colony formation abilities and proliferative, migrative, and invasive potentials of HCC cells were diminished, while cell cycle arrest and apoptosis were enhanced. Moreover, LINC01224 induced HCC progression in vitro and accelerated tumor formation in nude mice by increasing CHEK1 expression.The key findings of the present study demonstrated that silencing LINC01224 could downregulate the expression of CHEK1 by competitively binding to miR-330-5p, thus inhibiting HCC progression. This result highlights the LINC01224/miR-330-5p/CHEK1 axis as a novel molecular mechanism involved in the pathology of HCC.
The fact that increasing antibiotic resistance of pathogenic bacteria and a lack of new potent broad-spectrum antibiotics call for the development of alternative approaches for treating infectious diseases. With the merits of great efficacy, safety, and facile implementation, antibacterial photodynamic therapy (APDT) represents an attractive modality for this purpose. Here, we report that the newly fabricated photodynamic chitosan nano-assembly, designated CS-Ce6, could synergistically kill antibiotic-resistant bacteria with superior potency to vancomycin. CS-Ce6 nano-assembly, obtained from covalent conjugate of chlorin e6 (Ce6) with chitosan, exhibited strong association with bacteria, thus altering their morphologies and mediating great delivery efficiency of Ce6. Upon light irradiation, localized generation of singlet oxygen by CS-Ce6 nano-assembly has a remarkable bactericidal effect toward both drug-resistance Gram-positive methicillin-resistant Staphylococcus aureus (MRSA) and Gram-negative Acinetobacter baumannii, which was greater than that the free Ce6 and antibiotics had. We also confirmed that APDT-treated MRSA neither developed resistance to APDT nor altered their resistance to methicillin. Our in vivo studies demonstrated that the CS-Ce6 nano-assembly had comparable therapeutic efficacy with vancomycin in MRSA-infected mice. These results suggest that APDT by photodynamic chitosan nano-assembly hold great potential in combating antibiotic-resistant bacteria and hopefully in reducing the need of antibiotics in the future.
Background
Hepatocellular carcinoma (HCC) is one of the most common tumors globally, with varying prevalence based on endemic risk factors. Bone morphogenetic protein (BMP) exhibits a broad spectrum of biological activities in various tissues including angiogenesis. Here, this study aimed to investigate the mechanism of BMP2 in HCC by mediating the mitogen-activated protein kinase (MAPK)/p38 signaling pathway.
Methods
BMP2 expression was quantified in HCC and adjacent tissues. BMP2 gain- and loss-of-function experiments were conducted by infection with lentivirus over-expressing BMP2 or expressing shRNA against BMP2. The angiogenesis was evaluated with HepG2 cells co-cultured with ECV304 cells. SB-239063 was applied to inhibit the activation of the MAPK/p38 signaling pathway so as to identify the significance of this pathway in HCC progression. Finally, in vivo experiments were conducted to identify the role of BMP2 and the MAPK/p38 signaling pathway in tumor growth and angiogenesis.
Results
BMP2 was highly expressed in HCC. Over-expression of BMP2 was found to accelerate cell proliferation, migration, invasion, microvascular density, and angiogenesis and decrease cell apoptosis in vitro and in vivo. BMP2 silencing exhibited inhibitory effects on HCC cell invasion and angiogenesis. The co-culture system illustrated that HepG2 cells secreted BMP2 in ECV304, and silenced BMP2 in HepG2 cells resulted in the inactivation of the MAPK/p38 signaling pathway, thus suppressing cancer progression, tumor growth, and angiogenesis in HCC.
Conclusion
Taken together, the key findings of this study propose that silencing of BMP2 inhibits angiogenesis and tumor growth in HCC, highlighting BMP2 silencing as a potential strategy for the treatment of HCC.
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