The function of the blood-brain barrier (BBB) depends on the integrity of tight junction (TJ)-associated proteins. Netrin-1 is known to promote angiogenesis and may also regulate the BBB. To understand the association between netrin-1 and the TJ-associated proteins, the expression levels of proteins involved in maintaining the integrity of the BBB, including netrin-1, claudin-5, occludin and zonula occluden (ZO)-1, were investigated in the present study using quantitative polymerase chain reaction, western blot analysis and immunofluorescence. The aim of the present study was to determine the changes in BBB permeability and whether pZsGreen1-N1 mediated overexpression of netrin-1 increased the expression of the TJ-associated proteins following traumatic brain injury (TBI). The results demonstrated that the levels of mRNA transcription and protein expression of the TJ-associated proteins, claudin-5, occludin and ZO-1, were significantly reduced following TBI. Furthermore, the changes in the expression of these three TJ proteins were consistent with the changes in the BBB permeability, indicating that weakening intercellular junctions leads to BBB opening. The present study also demonstrated that netrin-1 significantly increased the downregulation of claudin-5, occludin and ZO-1 expression levels induced by TBI, which provided a basis for further investigation on the role of netrin-1 in the integrity of TJs and proper functioning of the BBB.
Background Long noncoding RNAs (lncRNA) are important in the growth and metastasis of colon cancer. The objective of this study was to describe the potential role of lncRNA NEAT1 in the progression of colon cancer. Methods Quantitative real‐time polymerase chain reaction was used for detecting NEAT1, miR‐185‐5p, and IGF2 in colon cancer cells and tissues. The potential diagnostic value of NEAT1 in colon cancer was analyzed with the receiver operating characteristic curve. Kaplan–Meier method was applied for evaluating the association between NEAT1 expression and the overall survival of osteosarcoma patients, whereas Transwell assay was introduced to examine the potential invasion and migration of colon cancer cells. In addition, the binding of NEAT1/IGF2 to miR‐185‐5p was confirmed by RNA pull‐down and RNA‐binding protein immunoprecipitation assays and dual‐luciferase reporter gene assay. Finally, rescue experiments were conducted to confirm the role of NEAT1/miR‐185‐5p/IGF2 axis in colon cancer. Results Colon cancer patients with low NEAT1 expression presented with longer overall survival than those with high expression. The migration and invasion of colon cancer cells were considerably promoted by overexpressed NEAT1. Both NEAT1 and IGF2 bound to miR‐185‐5p. Conclusion NEAT1 upregulate IGF2 expression through absorbing miR‐185‐5p to enhances the migration and invasion of colon cancer cells.
We have designed, synthesized and evaluated a series of new compounds based upon our previously reported bivalent Smac mimetics. This led to the identification of compound 12 (SM-1200), which binds to XIAP, cIAP1 and cIAP2 with Ki values of 0.5 nM, 3.7 nM and 5.4 nM, respectively, inhibits cell growth in the MDA-MB-231 breast cancer and SK-OV-3 ovarian cancer cell lines with IC50 values of 11.0 nM and 28.2 nM, respectively. Compound 12 has a much improved pharmacokinetic profile over our previously reported bivalent Smac mimetics and is highly effective in induction of rapid and durable tumor regression in the MDA-MB-231 xenograft model. These data indicate that compound 12 is a promising Smac mimetic and warrants extensive evaluation as a potential candidate for clinical development.
Gastric cancer is the third leading cause of cancer-associated mortality worldwide and is one of the most common malignancies in China. However, the molecular mechanisms underlying the tumorigenesis of gastric cancer remain largely unclear. Long non-coding (Lnc)RNAs have been demonstrated to serve significant roles in the tumorigenesis of various types of cancer. The present study aimed to explore the role of the LncRNA mediator of DNA damage checkpoint protein 1-antisense RNA (MDC1-AS), the antisense transcript of MDC1, in human gastric cancer. The results revealed that the expression of MDC1-AS in human gastric cancer was significantly suppressed in vivo and in vitro. In addition, overexpression of MDC1-AS in the poorly differentiated gastric cancer cell line MKN28 significantly inhibited cell proliferation and metastasis, while the knockdown of MDC1-AS in well-differentiated MKN45 gastric cancer cells significantly increased proliferation and metastasis. The knockdown of MDC1 relieved the inhibitory effect of MDC1-AS on MKN28 cell proliferation and metastasis, while the overexpression of MDC1 attenuated the stimulatory effect of MDC1-AS knockdown in MKN45 cells. Thus, the present study demonstrated that MDC1-AS had an inhibitory on gastric tumorigenesis through an MDC1-dependent mechanism. This indicates that MDC1-AS is a potential novel therapeutic target for the diagnosis and treatment of human gastric cancer in the clinic.
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