Feng Chi,Fang Qiu,Xiaoming Jin,Long Chen,Guijin He,Sijia Han
Breast cancer (BC) is one of the most frequently occurring malignant tumors in female adults. The long intergenic nonprotein coding RNA 00982 (LINC00982) has been regarded as a cancer suppressor in several human cancers. However, the function and the underlying mechanisms of LINC00982 have not been studied in BC. The present study found that LINC00982 was significantly downregulated in BC tumor tissues, and the low LINC00982 level predicts a poor prognosis of BC. Through the overexpression and suppression of LINC00982 in two BC cell lines, we found that LINC00982 could inhibit cell proliferation, migration, and invasion by suppressing the activity of the signal transducer and activator of transcription 3 (STAT3)/nuclear factor kappa B (NF-κB) signal pathway. Furthermore, luciferase reporter assay has been used to verify that LINC00982 functions as a molecular sponge for miR-765, which could target DPF3. The relative expression of miR-765 decreased with LINC00982 overexpressing, and DPF3 increased at the same time.In addition, the suppression of cell malignant phenotype caused by overexpression of LINC00982 can be reversed by inhibition of DPF3. To verify the function of LINC00982 in vivo, the BC cells were implanted in nude mice and the results suggested the tumor growth and malignant phenotype were suppressed by LINC00982. In this study, we prove that LINC00982 regulates the growth and development of BC through STAT3/NF-κB signal pathway, mediated by the miR-765/DPF3 axis. LINC00982 may function as a target molecule to take part in the prognosis and therapy of BC.
Juan Liu,Xiaomin Zhang,Kun Chen,Yujie Cheng,Shuxun Liu,Meng Xia,Yali Chen,Ha Zhu,Zhiqing Li,Xuetao Cao
Summary CCR7 chemokine receptor stimulation induces rapid but transient dendritic cell (DC) migration toward draining lymph nodes, which is critical for the initiation of protective immunity and maintenance of immune homeostasis. The mechanisms for terminating CCR7-mediated DC migration remain incompletely understood. Here we have identified a long non-coding RNA lnc-Dpf3 whose feedback restrained CCR7-mediated DC migration. CCR7 stimulation upregulated lnc-Dpf3 via removing N6-methyladenosine (m 6 A) modification to prevent RNA degradation. DC-specific lnc-Dpf3 deficiency increased CCR7-mediated DC migration, leading to exaggerated adaptive immune responses and inflammatory injuries. Mechanistically, CCR7 stimulation activated the HIF-1α transcription factor pathway in DCs, leading to metabolic reprogramming toward glycolysis for DC migration. lnc-Dpf3 directly bound to HIF-1α and suppressed HIF-1α-dependent transcription of the glycolytic gene Ldha , thus inhibiting DC glycolytic metabolism and migratory capacity. We demonstrate a critical role for CCR7-inducible lnc-Dpf3 in coupling epigenetic and metabolic pathways to feedback-control DC migration and inflammatory responses.
Yali Wu,Yunnan Ma,Wanling Zhong,Huijuan Shen,Jinhong Ye,Shouying Du,Pengyue Li
Ethnopharmacological relevance Thrombus generation is one of the leading causes of death in human, and vascular endothelial dysfunction is a major contributor to thrombosis. Pheretima guillemi (Michaelsen), a traditional medicinal animal known as “Dilong”, has been utilized to cure thrombotic disorders for many years. DPf3, a group of functional proteins extracted from P. guillemi , has been characterized and identified to possess antithrombotic bioactivity via in vitro and ex vivo experiments. Aim of the study This study is aimed to investigate the vascular-protection activity and related mechanism of antithrombotic protein DPf3 purified from Pheretima guillelmi systematically. Materials and methods The antithrombotic activity and vascular endothelium protection effect of DPf3 was explored in vivo using ponatinib-induced vascular endothelial injury zebrafish thrombus model. Then, (hi) ox-LDL-induced HUVECs was applied to investigate the protection mechanism of DPf3 against the injury of vascular endothelium. In addition, TMT-based proteomics analysis was used to study the biomarkers, biological processes and signal pathways involved in the antithrombotic and vascular protective effects of DPf3 holistically. Results DPf3 exerted robust in vivo antithrombosis and vascular endothelial protection ability. DPf3 was identified to prevent HUVECs from damage by reducing ROS production, and to reduce monocyte adhesion by decreasing the protein content of adhesion factor VCAM 1. DPf3 was also observed to weaken the migration ability of injured cells and inhibit abnormal angiogenesis. The mechanism of DPf3's antithrombotic and vascular protective activity was mainly related to the regulation of lipid metabolism, energy metabolism, complement and coagulation system, ECM receptor interaction, MAPK signal pathway, etc. Conclusions This study demonstrates that DPf3 has strong antithrombotic and endothelial protective effects. The endothelial protective ability and related mechanisms of DPf3 provide a scientific reference for the traditional use of earthworms in the treatment of thrombosis.
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