LncRNA NEAT1 Promotes Gastric Cancer Progression Through miR-17-5p/TGFβR2 Axis Up-Regulated Angiogenesis

Abstract

BackgroundLong non-coding RNAs (lncRNAs) have been indicated to play critical roles in gastric cancer (GC) tumorigenesis and progression. However, their roles in GC remain to be further elucidated.MethodsRT-qPCR and fluorescence in situ hybridzation (FISH) were conducted to detect the expression of lncRNA NEAT1 in GC tissues and cell lines. Gene Set Enrichment Analysis (GSEA) was performed to screen out potential phenotypes and pathways that NEAT1 may participate in. NEAT1-silenced AGS and MGC803 cells were constructed and a series of functional experiments to investigate the roles of NEAT1 in GC angiogenesis both in vitro and in vivo. RNA pull down and luciferase reporter assays were utilized to illustrate the mechanisms underlying the functions of NEAT1 in GC.ResultsWe observed that NEAT1 was upregulated in most GC specimens and cell lines. NEAT1 high was correlated with poor prognosis of GC patients. In vitro experiments showed that NEAT1 promoted GC angiogenesis by enhancing proliferation, migration, and tube formation ability of endothelial cells. Mechanism researches revealed that NEAT1 could competitively sponge miR-17-5p which targeted TGFβR2 directly. Subsequently, activate TGFβ/Smad pathway by following with upregulation of a series of classical proangiogenic factors especially VEGF.ConclusionThe study unveiled that the LncRNA NEAT1/miR-17-5p/TGFβR2 axis is a novel mechanism in GC angiogenesis. Disrupting this axis may be a potential strategy for GC treatment.

Multi-Omics Integration-Based Prioritisation of Competing Endogenous RNA Regulation Networks in Small Cell Lung Cancer: Molecular Characteristics and Drug Candidates

“…Here, we found that two lncRNAs (lncRNA-AC005005.4-201 and NEAT1-203) and two circRNAs (circRNA-hsa_HLA-B_1 and hsa_VEGFC_8) may regulate the inhibiting effects of hsa-miR-6747-3p for CSF3R expression, while lncRNA-DLX6-AS1-201 or circRNA-hsa_HLA-B_1 may neutralise the negative regulation of hsa- miR-4525 for GAA. Consistent with our findings for dysregulated lncRNAs in SCLC, previous studies found that lncRNAs DLX6-AS1 and NEAT1 were significantly dysregulated in non-SCLC, gastric cancer and pancreatic cancer (59)(60)(61)(62). Specifically, upregulated DLX6-AS1 in gastric cancer tissue associated with distant metastasis and a poor clinical prognosis, while siRNA-DLX6-AS1 may inhibit gastric cancer cell proliferation, migration, invasion and the epithelialmesenchymal transition in vitro (18).…”

“…Similar to the other dysregulated lncRNA reports ( 59 – 62 ), Xu et al. found that lncRNA-NEAT1 may promote gastric cancer angiogenesis by enhancing the proliferation, migration and tube formation ability of endothelial cells through the miR-17-5p/transforming growth factor-β receptor 2 (TGFβR2) pathway ( 61 ), while lncRNA-NEAT1 may play a vital role in tumorigenesis and the development of SCLC through the hsa-miR-6747-3p/CSF3R axis. Importantly, in addition to lncRNA-DLX6-AS1 and NEAT1, we are the first to report another potential regulatory axis of ceRNA, while the regulatory mechanisms require further exploration through in vivo and in vitro studies.…”

Oxidative stress-induced endothelial cells-derived exosomes accelerate skin flap survival through Lnc NEAT1-mediated promotion of endothelial progenitor cell function

“…With the use of a Wnt activator, the inhibitory effect of Lnc NEAT1 on EPCs function was partially alleviated. The phenomenon could be deciphered that Lnc NEAT1 participate in angiogenesis through multiple signaling pathways [ 56 – 58 ]. Yangwei Xu et al[ 56 ] demonstrated that LncRNA NEAT1 promoted gastric cancer progression through miR-17-5p/TGFβR2 axis up-regulated angiogenesis.…”

“…The phenomenon could be deciphered that Lnc NEAT1 participate in angiogenesis through multiple signaling pathways [ 56 – 58 ]. Yangwei Xu et al[ 56 ] demonstrated that LncRNA NEAT1 promoted gastric cancer progression through miR-17-5p/TGFβR2 axis up-regulated angiogenesis. Lidong Zhao et al[ 57 ] also found that Lnc NEAT1 promoted trophoblast proliferation and invasion in gestational hypertension and alleviated vascular endothelial injury by inhibiting miRNA-205-5p.…”

Construction of a Prognostic Model Based on Cuproptosis-Related lncRNA Signatures in Pancreatic Cancer

“…MALAT1 is one of the most abundant lncRNAs in normal tissues, and emerging evidence has linked MALAT1 to lung cancer, breast cancer, prostate cancer, and pancreatic cancer [29]. In pancreatic cancer, importin 7 (a nuclear transport factor) inhibits the expression of p53 and induces the expression of MALAT1, resulting in the progression of pancreatic cancer [30]. LINC01963 is expressed at lower levels in pancreatic cancer tissues and cell lines.…”