Long Noncoding RNA Nuclear Paraspeckle Assembly Transcript 1 Promotes Progression and Angiogenesis of Esophageal Squamous Cell Carcinoma Through miR-590-3p/MDM2 Axis

Abstract

Angiogenesis has been identified as one of the hallmarks of cancer and aggravates cancer development and progression. Accumulating evidence indicated that long noncoding RNAs (lncRNAs) are powerful factors in regulating various cancer behaviors. The aim of this study is to verify the function and potential mechanisms of lncRNA NEAT1 in progression and angiogenesis of esophageal squamous cell carcinoma (ESCC). We found that NEAT1 was overexpressed in ESCC tissues and correlated with clinical characteristics of patients. Silence of NEAT1 inhibited proliferation, migration, invasion and angiogenesis of ESCC cells. High throughput sequencing and western blotting revealed that NEAT1 regulated MDM2/p53 pathway. Rescue of MDM2 restored the effect of NEAT1 on progression and angiogenesis of ESCC cells. Nude mice xenograft models further validated the role of NEAT1 in vivo. Importantly, NEAT1 functioned as a competing endogenous RNA for miR-590-3p to regulate MDM2 expression and miR-590-3p acted as a tumor suppressor in ESCC progression and angiogenesis. These findings suggested that NEAT1/miR-590-3p/MDM2 axis might serve as potential therapeutic targets for ESCC patients.

Systematical identification of key genes and regulatory genetic variants associated with prognosis of esophageal squamous cell carcinoma

“…[73][74][75] Previous studies have found that NEAT1 promotes angiogenesis and tumor progression by regulating miR-590-3p or miR-129 or miR-377 in ESCC. [76][77][78] Here, our study added to the knowledge of NEAT1 and cancer progression and outcome.…”

Long Non-coding RNAs Sponging MicroRNAs With Efficacy in Preclinical In Vivo Models of Esophageal Squamous Cell Cancer

“…LncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) targets mouse double minute homolog 2 (MDM2). LncRNA NEAT1 (Figure 5) was highly expressed in ESCC tissues and correlated with lymph node metastasis and distant metastasis (160). NEAT1 promoted proliferation, invasion, migration, and angiogenesis in Eca109 and TE13 ESCC cells and human umbilical vein endothelial cells in vitro (161).…”

“…NEAT1 promoted proliferation, invasion, migration, and angiogenesis in Eca109 and TE13 ESCC cells and human umbilical vein endothelial cells in vitro (161). Knockdown of NEAT1 inhibited growth of Eca 109 xenografts in vivo in nude mice (160). NEAT1 sponged miR-590-3p resulting in up-regulation of MDM2 (160).…”

“…Knockdown of NEAT1 inhibited growth of Eca 109 xenografts in vivo in nude mice (160). NEAT1 sponged miR-590-3p resulting in up-regulation of MDM2 (160). MDM2 is a proto-oncogene which promotes tumor formation by targeting p53 for degradation and is amplified in several types of tumors (161,162).…”

Long non‐coding RNA ESCCAL‐1/miR‐590/LRP6 signaling pathway participates in the progression of esophageal squamous cell carcinoma

“…They play essential roles in a variety of tumors. 12 MiR‐590 was reported to be a suppressor of breast cancer (BC), 13 ESCC, 14 non‐small cell lung cancer (NSCLC), 15 hepatocellular carcinoma (HCC), 16 osteosarcoma, 17 pancreatic cancer, 18 and colorectal cancer (CRC). 19 Here, miR‐590 showed down‐regulation within ESCC.…”