Knockdown of long non-coding RNA XIST increases blood–tumor barrier permeability and inhibits glioma angiogenesis by targeting miR-137

Abstract

Antiangiogenic therapy plays a significant role in combined glioma treatment. However, poor permeability of the blood–tumor barrier (BTB) limits the transport of chemotherapeutic agents, including antiangiogenic drugs, into tumor tissues. Long non-coding RNAs (lncRNAs) have been implicated in various diseases, especially malignant tumors. The present study found that lncRNA X-inactive-specific transcript (XIST) was upregulated in endothelial cells that were obtained in a BTB model in vitro. XIST knockdown increased BTB permeability and inhibited glioma angiogenesis. The analysis of the mechanism of action revealed that the reduction of XIST inhibited the expression of the transcription factor forkhead box C1 (FOXC1) and zonula occludens 2 (ZO-2) by upregulating miR-137. FOXC1 decreased BTB permeability by increasing the promoter activity and expression of ZO-1 and occludin, and promoted glioma angiogenesis by increasing the promoter activity and expression of chemokine (C–X–C motif) receptor 7b (CXCR7). Overall, the present study demonstrates that XIST plays a pivotal role in BTB permeability and glioma angiogenesis, and the inhibition of XIST may be a potential target for the clinical management of glioma.

Overexpressed microRNA‐103a‐3p inhibits acute lower‐extremity deep venous thrombosis via inhibition of CXCL12

“…30 Furthermore, miR-26a inactivates the NF-κB signaling pathway by binding PRKCD mRNA and downregulates the levels of inflammatory chemokines CCL2 and CCL7, thereby suppressing the risk of DVT. 31 Subsequently, we found that overexpressed miR-103a-3p downregulated CXCL12 expression to reduce inflammatory response and thrombosis, which was verified by decreased IL-6, IL-8, and TF, PAIs, vWF, and TH-A2 expression in response to miR-103a-3p agomir injection in mice. Previous evidence has demonstrated that downregulation of certain inflammatory cytokines, including IL-6 and IL-8, is closely associated with alleviated inflammation in DVT.…”

“…miR‐126, on the other hand, inhibits its target PIK3R2 gene expression, which acts to inhibit thrombus formation in vivo . Furthermore, miR‐26a inactivates the NF‐κB signaling pathway by binding PRKCD mRNA and downregulates the levels of inflammatory chemokines CCL2 and CCL7, thereby suppressing the risk of DVT …”

lncRNA FAM83H‑AS1 is associated with the prognosis of colorectal carcinoma and promotes cell proliferation by targeting the Notch signaling pathway

“…lncRNAs have been reported to be involved in a variety of biological processes, including tumorigenesis through regulating oncogenes or tumor suppressors at several levels (3)(4)(5)(6)(7)(8)(9)(10)(11)(12). For example, Xia et al (13) demonstrated that long noncoding RNA papillary thyroid carcinoma susceptibility candidate 3 (PTCSC3) inhibited proliferation and invasion of glioma cells by suppressing the Wnt/β-catenin signaling pathway.…”

lncRNA SNHG5 is associated with poor prognosis of bladder cancer and promotes bladder cancer cell proliferation through targeting p27

“…Currently, long non-coding RNAs (lncRNAs), newly identified members of the noncoding RNA family with length >200 nucleotides (nt), have been proposed (2)(3)(4). Accumulating documents have revealed that lncRNAs play a critical role in tumorigenesis and can be used as biomarkers for diagnosis or prediction of survival and recurrence in multiple cancers (5)(6)(7)(8)(9).…”