Arsenic exposure is associated with lung cancer. Angiogenesis is essential for tumor development. However, the role and mechanism of human vascular endothelial cells in tumor growth and angiogenesis induced by arsenic-transformed bronchial epithelial (As-T) cells remain to be elucidated. In this study, we found that endothelial cells significantly increased As-T cell-induced tumor growth compared to those induced by As-T cells alone. To understand the molecular mechanism, we found that endothelial cells co-cultured with As-T cells or cultured in conditioned medium (CM) prepared from As-T cells showed much higher cell migration, proliferation, and tube formation compared to those co-cultured with BEAS-2B (B2B) cells or cultured in CM from B2B. We identified that higher levels of intracellular interleukin 8 (IL-8) were secreted by As-T cells, which activated IL-8/IL-8R signaling to promote endothelial cells migration and tube formation. IL-8 silencing and knockout (KO) in As-T cells, or IL-8 neutralizing antibody dramatically suppressed endothelial cell proliferation, migration, tube formation in vitro, and tumor growth and angiogenesis in vivo, suggesting a key role of IL-8 in As-T cells to induce angiogenesis via a paracrine effect. Finally, blocking of IL-8 receptors C-X-C chemokine receptor type 1 (CXCR1) and CXCR2 with neutralizing antibodies and chemical inhibitors inhibited tube formation, indicating that IL-8Rs on endothelial cells are necessary for As-T cell-induced angiogenesis. Overall, this study reveals an important molecular mechanism of arsenic-induced carcinogenesis, and suggests a new option to prevent and treat arsenic-induced angiogenesis.

This study aims to explore the role of hyperlipidemia in the mobilization of bone marrow (BM) endothelial progenitor cells (EPCs) induced by acute myocardial ischemia (AMI). To establish the hyperlipidemia complicated with AMI (HL-AMI) model, SD rats were intragastrically administered the high-fat emulsion for 4 weeks. Then their left anterior descending arteries were ligated. Rats in each group were randomly subdivided into seven subgroups. During 1st ~ 7th day following AMI modeling, rats in 1st ~ 7th subgroups were selected to be phlebotomized from their celiac artery after being anesthetized by pentobarbitone in turn. The quantity of circulating EPCs (CEPCs) was detected by flow cytometry, the expression of VEGF, eNOS, NO, MMP-9 in myocardial tissue was analyzed by western blot, and their plasma level was assayed by ELISA. Dynamic curves were plotted using these data. Within 7 days following AMI, compared with the AMI rats, in the HL-AMI rats, the myocardial infarct size, the plasma activity of CK, CK-MB, and the collagen deposition all remained at the higher levels; meanwhile, these rats showed more significant decreases in the count of CEPCs, the plasma level of VEGF etc., and their expression in myocardial tissue (P < 0.05 or P < 0.01). Our study showed that hyperlipidemia may attenuate the mobilization of BM EPCs induced by AMI via VEGF/eNOS/NO/MMP-9 signal pathway, which might partly account for hyperlipidemia hampering the repairs of AMI-induced cardiac injury.

Acute kidney injury (AKI) is a common renal dysfunction. Renal ischemia-reperfusion (I/R) injury contributes to AKI progression. The microRNA miR-195-5p can act as a crucial tumor inhibitor in various cancers. However, the potential biological effects of miR-195-5p on AKI are not well-understood. We found that miR-195-5p levels were decreased in the serum samples of patients with AKI. Next, we determined miR-195-5p expression in the renal tissues of the rats and found that it was downregulated. Renal function was evaluated and confirmed using blood urea nitrogen and serum Cr levels. In parallel, the hypoxia-induced NRK-52E cell model was employed, and miR-195-5p was found to be markedly reduced under hypoxic conditions. Furthermore, miR-195-5p was modulated in NRK-52E cells. miR-195-5p induced NRK-52E cell proliferation and protected NRK-52E cells against hypoxia-triggered apoptosis. In an I/R mouse model, miR-195-5p alleviated renal injury triggered by I/R. In addition, oxidative stress and inflammatory factor concentrations were assessed using ELISA. The results showed that miR-195-5p mimicked attenuated oxidative stress induced by I/R injury and downregulated the protein expression of inflammatory factors. Moreover, we identified that vascular endothelial growth factor A (VEGFA) was a target gene of miR-195-5p, which could negatively regulate VEGFA expression in vitro. Inhibitors of miR-195-5p subsequently contributed to renal injury, which was reversed by VEGFA loss. In conclusion, miR-195-5p may repress AKI by targeting VEGFA.

Bladder cancer (BC) is one of the most commonly diagnosed urologic carcinomas, with high recurrence and death rates. Circular RNAs (circRNAs) are a class of noncoding RNAs which are anomalously expressed in cancers and involved in the progression of cancers. In this study, we found that circSEMA5A was upregulated in BC tissues and cell lines. The overexpressed circSEMA5A was correlated with malignant characteristics of BC. In vitro data indicated that circSEMA5A promoted proliferation, suppressed apoptosis, facilitated migration, accelerated invasion, enhanced angiogenesis and promotes glycolysis of BC. Mechanistically, circSEMA5A served as a miRNA sponge for miR-330-5p to upregulates Enolase 1 (ENO1) expression and facilitated the activation of Akt and β-catenin signaling pathways. Then, we showed that circSEMA5A exerted its biological functions partially via miR-330-5p/ENO1 signaling. Moreover, circSEMA5A raised SEMA5A expression by recruiting EIF4A3 to enhance the mRNA stability of SEMA5A, and thereby accelerated BC angiogenesis. To sum up, circSEMA5A is upregulated in BC and facilitates BC progression by mediating miR-330-5p/ENO1 signaling and upregulating SEMA5A expression.