• Journal of Microbiology and Biotechnology
• /
• v.34 no.7
• /
• pp.1433-1442
• /
• 2024

Gastric adenocarcinoma (GAC) is a common, malignant type of tumor in human, and is accompanied with higher mortality. Muscleblind-like 3 (MBNL3) was found to be a pivotal participator in aggravating this cancer's progression. However, the regulatory effects of MBNL3 on GAC development have not been investigated. We therefore sought to study the functions of MBNL3 in GAC progression. In this study, it was demonstrated that MBNL3 exhibited higher expression, and GAC patients with higher MBNL3 expression had poor prognosis. Overexpression of MBNL3 facilitated, and knockdown of MBNL3 suppressed cell proliferation, invasion, and angiogenesis in GAC. Further experiments showed that miR-302e targets MBNL3. Rescue assays then uncovered that the miR-302e/MBNL3 axis aggravated GAC progression. In addition, MBNL3 activated the AKT/VEGFA pathway, and the suppressive regulatory impacts of MBNL3 knockdown on GAC cell proliferation, invasion, and angiogenesis could be rescued after 740 Y-P treatment. Through in vivo assay, it was proved that MBNL3 accelerated tumor growth in vivo. In conclusion, MBNL3 acted as a target of miR-302e to facilitate cell proliferation, invasion, and angiogenesis of gastric adenocarcinoma through the AKT/VEGFA pathway. Our findings illustrate that MBNL3 may be an available bio-target for GAC treatment.

• Journal of Microbiology and Biotechnology
• /
• v.34 no.7
• /
• pp.1410-1418
• /
• 2024

Alveolar echinococcosis (AE) is a persistent parasite condition that causes the formation of tumorlike growths. It is a challenge to treat the disease. These growths need neovascularization to get their oxygen and nutrients, and the disease is prolonged and severe. Considerable research has been conducted on exosomes and their interactions with Echinococcus multilocularis in the context of immunological evasion by the host. However, the extent of their involvement in angiogenesis needs to be conducted. The primary objective of this investigation was to preliminarily explore the effect of exosomes produced from E. multilocularis protoscoleces (PSC-exo) on angiogenesis, to elucidate the mechanism of their roles in the regulation of the downstream pathway of VEGFA activation, and to provide ideas for the development of novel treatments for AE. The study evaluated the impact of PSC-exo increases proliferation, migration, invasion, and tube formation of HUVECs at concentrations of up to 50 ㎍/ml. In addition, the study sought to validate the findings in vivo. This effect involved increased VEGFA expression at gene and protein levels and AKT/mTOR pathway activation. PSC-exo are crucial in promoting angiogenesis through VEGFA upregulation and AKT/mTOR signaling. This research contributes to our knowledge of neovascularization in AE.

• BMB Reports
• /
• v.57 no.5
• /
• pp.244-249
• /
• 2024

Many types of cancer are associated with excessive angiogenesis. Anti-angiogenic treatment is an effective strategy for treating solid cancers. This study aimed to demonstrate the inhibitory effects of (E)-2-methoxy-4-(3-(4-methoxyphenyl) prop-1-en-1-yl) phenol (MMPP) in VEGFA-induced angiogenesis. The results indicated that MMPP effectively suppressed various angiogenic processes, such as cell migration, invasion, tube formation, and sprouting of new vessels in human umbilical vein endothelial cells (HUVECs) and mouse aortic ring. The inhibitory mechanism of MMPP on angiogenesis involves targeting VEGFR2. MMPP showed high binding affinity for the VEGFR2 ATP-binding domain. Additionally, MMPP improved VEGFR2 thermal stability and inhibited VEGFR2 kinase activity, suppressing the downstream VEGFR2/AKT/ERK pathway. MMPP attenuated the activation and nuclear translocation of NF-κB, and it downregulated NF-κB target genes such as VEGFA, VEGFR2, MMP2, and MMP9. Furthermore, conditioned medium from MMPP-treated breast cancer cells effectively inhibited angiogenesis in endothelial cells. These results suggested that MMPP had great promise as a novel VEGFR2 inhibitor with potent anti-angiogenic properties for cancer treatment via VEGFR2/AKT/ERK/NF-κB signaling pathway.