RhoC/ROCK2 promotes vasculogenic mimicry formation primarily through ERK/MMPs in hepatocellular carcinoma

Vasculogenic mimicry (VM) results in the formation of an alternative circulatory system that can improve the blood supply to multiple malignant tumors, including hepatocellular carcinoma (HCC). However, the potential mechanisms of RhoC/ROCK in VM have not yet been investigated in HCC. Here, RhoC expression was upregulated in HCC tissues, especially the VM-positive (VM+) group, compared to noncancerous tissues (P < 0.01), and patients with high expression of RhoC had shorter survival times (P < 0.001). The knockdown of RhoC via short hairpin RNA (shRNA) in SK-Hep-1 cells significantly decreased VM formation and cell motility. In contrast, cell motility and VM formation were remarkably enhanced when RhoC was overexpressed in HepG2 cells. To further assess the potential role of ROCK1 and ROCK2 on VM, we stably knocked down ROCK1 or ROCK2 in MHCC97H cells. Compared to ROCK1 shRNA, ROCK2 shRNA could largely affect VM formation, cell motility and the key VM factors, as well as the epithelial-mesenchymal transition (EMT) markers in vitro and in vivo. Moreover, p-ERK, p-MEK, p-FAK, p-paxillin, MT1-MMP and MMP2 levels were clearly altered following the overexpression of RhoC, but ROCK2 shRNA had little effect on the expression of p-FAK, which indicated that RhoC regulates FAK/paxillin signaling, but not through ROCK2. In conclusion, our results show that RhoC/ROCK2 may have a major effect on VM in HCC via ERK/MMPs signaling and might be a potential therapeutic target for the treatment of HCC.     

Epstein–Barr virus noncoding RNAs from the extracellular vesicles of nasopharyngeal carcinoma (NPC) cells promote angiogenesis via TLR3/RIG-I-mediated VCAM-1 expression

Viral noncoding RNAs (Epstein–Barr virus-encoded RNAs, EBERs) are believed to play a critical role in the progression of lymphoma and nasopharyngeal carcinoma (NPC). However, the accurate mechanisms accounting for their oncogenic function have not been elucidated, especially in terms of interaction between tumor cells and mesenchymal cells. Here, we report that, in addition to NPC cells, EBERs are also found in endothelial cells in Epstein–Barr virus (EBV)-infected NPC parenchymal tissues, which implicates NPC-derived extracellular vesicles (EVs) in transmitting EBERs to endothelial cells. In support of this hypothesis, we first ascertained if EBERs could be transferred to endothelial cells via EVs isolated from NPC culture supernatant. Then, we clarified that EVs-derived EBERs could promote angiogenesis through stimulation of VCAM-1 expression. Finally, we explored the involvement of EBER recognition by TLR3 and RIG-I in NPC angiogenesis. Our observations collectively illustrate the significance and mechanism of EVs-derived EBERs in angiogenesis and underlie the interaction mechanisms between EBV-infected NPC cells and the tumor microenvironment.     

Retracted: KDM6B promotes ovarian cancer cell migration and invasion by induced transforming growth factor-β1 expression

KDM6B, also known as JMJD3, is a member of the family of histone lysine demethylase (KDMs), which is closely related to many types of cancers. However, its role and the underlying mechanisms in ovarian cancer remain unknown. Here we show that KDM6B is elevated in epithelial ovarian cancer and its expression level is closely related with metastasis and invasion. In addition, survival analysis showed that high expression of KDM6B was associated with low overall survival in ovarian cancer patients. Overexpression of KDM6B in epithelial ovarian cancer cells promoted proliferation, epithelial-mesenchymal transition (EMT), migration and invasion in vitro, and enhanced metastatic capacities in vivo. On the contrary, silencing KDM6B in invasive and metastatic ovarian cancer cells inhibited these processes. Mechanistically, we found that KDM6B exerts its function by modulating the transforming growth factor-β1 (TGF-β1) expression, and TGF-β1 signal pathway inhibitor LY2157299 significantly inhibited KDM6B-induced proliferation, migration, metastasis, and EMT in ovarian cancer cells. Our findings, for the first time, reveal the pivotal role of KDM6B in the invasion and metastatic behavior of epithelial ovarian cancer. Thus, targeting KDM6B may be a useful strategy to interfere with these behaviors of epithelial ovarian cancer.     

Global distribution and invasion pattern of oriental fruit fly,Bactrocera dorsalis (Diptera: Tephritidae)

Since the start of the 20th century, many invasive alien species (IAS) have spread rapidly around the world, causing serious threats to economies, societies and the environment. Bactrocera dorsalis (Hendel) (Diptera: Tephritidae) is an important quarantine insect species in many countries that spread around the world over the last century. This review collected information on the distribution of B. dorsalis to explore the patterns of its invasion expansion. We found B. dorsalis to be distributed in 75 countries (comprised of 124 geographical distribution regions: provinces or states) in Asia, Africa, North America, South America and Oceania up to 2017. Asia and Africa were the most represented regions, accounting for 86.3% of the total number of countries. From 1910 to 1990, B. dorsalis was only found in five countries, but in the last three decades, it has experienced a sharp increase in its rate of spread, invading 70 more countries. Global temperature anomaly has significantly positive correlation with the spread of B. dorsalis. The results of this review provide a theoretical basis for understanding and predicting the continued spread of B. dorsalis under global changes.     

Optic nerve-dependent changes in adult frog tectal cell phenotypes

Optic nerve activity helps determine the placement of retinal ganglion cell terminals in the optic tectum of the frog. We investigated whether the presence of this nerve might also influence a characteristic of its target structure, neurotransmitter biosynthesis. We performed unilateral optic nerve transections on adult animals and assayed the percent and intensity of substance P- and serotoninlike immunoreactive (SP-ir and 5-HT-ir, respectively) cells in the deafferented and afferented tectal lobes. Regeneration of the optic nerve was prevented. The percent of SP-ir cells in the afferented tectal lobes was significantly less than that in the deafferented ones either 6 weeks or 5 months following optic nerve lesion. Comparison to normal animals indicated that the change in SP-ir expression was due to a decrease in the percent of immunoreactive cells in the afferented tecta ipsilateral to the optic nerve lesion. The serotoninlike immunoreactivity of tectal cells was also significantly different in the two lobes following optic nerve lesions. This difference resulted from an increase in the percent of 5-HT-ir cells in the deafferented tectum. In addition, the intensity of 5-HT-ir cells in the deafferented lobe was significantly greater than in the afferented one. The staining intensity of SP-ir cells underwent only a transient, relative decrease in the deafferented tectum. We conclude that the optic nerve does regulate substance P and serotonin expression in the tectum, but that this regulation likely occurs through different pathways. © 1996 John Wiley & Sons, Inc.     

Structural basis for the recognition of methylated histone H3 by the Arabidopsis LHP1 chromodomain

Arabidopsis LHP1 (LIKE HETEROCHROMATIN PROTEIN 1), a unique homolog of HP1 in Drosophila, plays important roles in plant development, growth, and architecture. In contrast to specific binding of the HP1 chromodomain to methylated H3K9 histone tails, the chromodomain of LHP1 has been shown to bind to both methylated H3K9 and H3K27 histone tails, and LHP1 carries out its function mainly via its interaction with these two epigenetic marks. However, the molecular mechanism for the recognition of methylated histone H3K9/27 by the LHP1 chromodomain is still unknown. In this study, we characterized the binding ability of LHP1 to histone H3K9 and H3K27 peptides and found that the chromodomain of LHP1 binds to histone H3K9me2/3 and H3K27me2/3 peptides with comparable affinities, although it exhibited no binding or weak binding to unmodified or monomethylated H3K9/K27 peptides. Our crystal structures of the LHP1 chromodomain in peptide-free and peptide-bound forms coupled with mutagenesis studies reveal that the chromodomain of LHP1 bears a slightly different chromodomain architecture and recognizes methylated H3K9 and H3K27 peptides via a hydrophobic clasp, similar to the chromodomains of human Polycomb proteins, which could not be explained only based on primary structure analysis. Our binding and structural studies of the LHP1 chromodomain illuminate a conserved ligand interaction mode between chromodomains of both animals and plants, and shed light on further functional study of the LHP1 protein.