The LncRNA NEAT1 Accelerates Lung Adenocarcinoma Deterioration and Binds to Mir-193a-3p as a Competitive Endogenous RNA

Abstract

Background/Aims: Long noncoding RNAs (lncRNAs) contribute to the development of multiple malignant tumors. Here, we focused on the biological function and underlying molecular mechanism of an lncRNA, nuclear-enriched abundant transcript 1 (NEAT1), in lung adenocarcinoma (LUAD). Methods: In vitro experiments were conducted to determine the biological effects of NEAT1 in LUAD cells. A luciferase activity reporter assay was performed to corroborate the interaction between NEAT1 and miR-193a-3p. Data from Gene Expression Omnibus (GEO), Oncomine, The Cancer Genome Atlas (TCGA), and our in-house reverse transcription quantitative PCR (RT-qPCR) were combined to examine the expression of NEAT1 and miR-193a-3p in LUAD. To further explore the regulatory mechanism of NEAT1, we searched for putative target genes of miR-193a-3p from 12 online prediction databases and determined genes positively correlated with NEAT1 as candidate targets. Furthermore, we analyzed the expression of these selected genes using data from TCGA. Results: In vitro experiments showed that knockdown of NEAT1 in LUAD cells markedly restrained cell proliferation, invasion, and migration and stimulated cell apoptosis. The dual-luciferase reporter assay demonstrated that miR-193a-3p directly targeted NEAT1 at its 3’-UTR. We then detected NEAT1 and miR-193a-3p in LUAD cells and normal lung epithelial cells and discovered high expression of NEAT1 and low expression of miR-193a-3p in LUAD cell lines. Simultaneously, the pooled results from the GEO, Oncomine, TCGA, and in-house RT-qPCR showed that the NEAT1 expression increased while the miR-193a-3p expression decreased in LUAD tissues versus normal lung tissues. Furthermore, the USF1 gene was not only upregulated in LUAD, but also positively correlated with NEAT1, suggesting that NEAT1 may function as a ceRNA to sponge miR-193a-3p and abrogate the inhibitory effect of miR-193a-3p on USF1. Conclusions: Our findings indicate that NEAT1 plays important roles in the occurrence and progression of LUAD. It may exert its role by acting as a ceRNA to regulate miR-193a-3p.

MSC-derived exosomes promote proliferation and inhibit apoptosis of chondrocytes via lncRNA-KLF3-AS1/miR-206/GIT1 axis in osteoarthritis

“…LncRNAs have been well known to exert roles by acting as a competitive endogenous RNA (ceRNA) to segregate microRNAs (miRNAs) away from target mRNAs [15][16][17]. Using bioformatics analysis, we noted that KLF3-AS1 harbors putative binding sites of miR-206.…”

“…Furthermore, GIT1 was identified as a putative target of miR-206 by harboring a miR-206 binding sequence in the 3ʹ-UTR of its mRNA (Targetscan). LncRNAs have been well known to exert roles by acting as a competitive endogenous RNA (ceRNA) to segregate microRNAs (miRNAs) away from target mRNAs [15][16][17]. Therefore, we speculated that, exosomal KLF3-AS1 derived from MSCs might act as a ceRNA by sponging miR-206 to facilitate GIT1 expression, and thereby promote chondrocyte proliferation and inhibit chondrocyte apoptosis.…”

<p>MIR22HG As A Tumor Suppressive lncRNA In HCC: A Comprehensive Analysis Integrating RT-qPCR, mRNA-Seq, And Microarrays</p>

“…The process of qRT-PCR has been described in detail in previous studies. [17][18][19] GAPDH served as the reference gene for MIR22HG. Information about the primers for MIR22HG and GAPDH is listed in Table 1.…”

Long noncoding RNA HOTTIP is associated with male infertility and promotes testicular embryonal carcinoma cell proliferation

“…For instance, Feng K et al identified that the viability and invasion of papillary thyroid carcinoma cells can be enhanced by lncRNA PVT1 , a ceRNA of miR‐30a, mediating IGF1 receptor expression (Feng et al, ). Yang et al reported that lncRNA HOTTIP accelerates the migration and proliferation of prostate cancer cells by sponging miR‐216a‐5p (Xiong et al, ). After the intersection of bioinformatics prediction results, it was discovered that miR‐128‐3p was highly consistent with HOTTIP ’s 3’UTR sequence.…”