Downregulation of lncRNA NEAT1 inhibits the proliferation of human cutaneous squamous cell carcinoma in vivo and in vitro

Abstract

Background: The incidence of cutaneous squamous cell carcinoma (CSCC), a malignant tumor that threatens human life, is increasing every year, and yet its pathogenesis is still unclear. This study found that long noncoding RNA (lncRNA) nuclear-enriched abundant transcript 1 (NEAT1) was abnormally expressed in CSCC. However, the biochemical mechanisms of lncRNA NEAT1 in carcinogenesis and the development of cancer remain unclear.Methods: Fluorescence quantitative polymerase chain reaction (qPCR) was conducted to determine lncRNA NEAT1 expression in CSCC and paracarcinoma tissues and investigate the correlation between NEAT1 levels and patients' clinicopathological features. The invasion, proliferation, and migration of CSCC cells were measured using colony formation, Cell Counting Kit-8, and Transwell assays. Western blot assay was conducted to test whether NEAT1 knockdown affected invasion and migration-related proteins. In addition, a nude mouse subcutaneous tumorigenesis experiment was performed to determine whether the knockdown of NEAT1 affected the proliferation ability of CSCC cells.Results: Changes in lncRNA NEAT1 expression in CSCC tissues were correlated with the degree of lymph node metastasis and the tumor, regional lymph nodes, and distant metastasis (TNM) grade of patients. The downregulation of NEAT1 lncRNA significantly impeded cell invasion, proliferation, and migration in CSCC. Through lncRNA NEAT1 knockdown, significant reductions in metalloproteinase-2, metalloproteinase-9, N-cadherin, and vimentin expression were observed, and the level of E-cadherin increased. In vivo experiments in nude mice revealed that knockdown of lncRNA NEAT1 greatly inhibited cell proliferation in CSCC. Conclusions:In CSCC tissues, NEAT1 lncRNA was expressed at high levels and correlated with lymph node metastasis and TNM stage. The knockdown of NEAT1 lncRNA could significantly impede CSCC proliferation, metastasis, and invasion. Additionally, by measuring the expression level of lncRNA NEAT1, we may be able to detect the clinical and pathological characteristics of CSCC.

Super Enhancer-Regulated LINC00094 (SERLOC) Upregulates the Expression of MMP-1 and MMP-13 and Promotes Invasion of Cutaneous Squamous Cell Carcinoma

“…On the other hand, PRECSIT has been shown to increase the invasion of cSCC cells by regulating the expression of MMPs via STAT3 signaling [ 18 ]. Additionally, recent studies have implicated lncRNAs HOTAIR [ 38 ], NEAT1 [ 39 ], and MALAT1 [ 40 ] in the progression of cSCC. Furthermore, LINC00319 has been noted to regulate the invasion of cSCC cells [ 41 ].…”

LncRNA NEAT1 Targets miR-342-3p/CUL4B to Inhibit the Proliferation of Cutaneous Squamous Cell Carcinoma Cells

“…in CSCC Tissues. Our previous study demonstrated that lncRNA NEAT1 was overexpressed in CSCC tissues [11].…”

“…As colorectal cancer development and metastasis are facilitated by the stimulation of the Wnt signaling pathway activated through lncRNA NEAT1, the lncRNA NEAT1/DDX5/Wnt/-catenin axis might be an effective therapeutic target [10]. Knockdown of lncRNA NEAT1 was demonstrated to significantly decrease the proliferation and invasion of CSCC [11]. However, the mechanism by which lncRNA NEAT1 controls cell proliferation and invasion is still unknown.…”

Contribution of Non-Coding RNAs to Anticancer Effects of Dietary Polyphenols: Chlorogenic Acid, Curcumin, Epigallocatechin-3-Gallate, Genistein, Quercetin and Resveratrol

“…LncRs are more than 200 bases long and are species/tissue specific. LncRs can interact with DNA, RNA, and proteins to regulate a wide range of biological processes [ 149 , 150 ]. Recent microarray analyses and next-generation sequencing assays have found that lncRs can modulate gene expression at multiple levels, including regulation at the epigenetic, transcriptional, and post-transcriptional levels.…”