Long noncoding RNA NEAT1 promotes laryngeal squamous cell cancer through regulating miR-107/CDK6 pathway

Abstract

BackgroundLong noncoding RNA nuclear paraspeckle assembly transcript 1 (NEAT1) plays key role in the progression of some human cancers. However, the role of NEAT1 in human laryngeal squamous cell cancer (LSCC) is still unknown. We therefore investigated the expression and function of NEAT1 in LSCC.MethodsNEAT1 level in LSCC and adjacent non-neoplastic tissues were detected by qRT-PCR. NEAT1 was knockdown in LSCC cells and cell proliferation, apoptosis and cell cycle were examined. The growth of xenografts with NEAT1 knockdown LSCC cells was analyzed.ResultsNEAT1 level was significantly higher in LSCC than in corresponding adjacent non-neoplastic tissues, and patients with neck nodal metastasis or advanced clinical stage had higher NEAT1 expression. Moreover, siRNA mediated NEAT1 knockdown significantly inhibited the proliferation and induced apoptosis and cell cycle arrest at G1 phase in LSCC cells. The growth of LSCC xenografts was significantly suppressed by the injection of NEAT1 siRNA lentivirus. Furthermore, NEAT1 regulated CDK6 expression in LSCC cells which was mediated by miR-107.ConclusionNEAT1 plays an oncogenic role in the tumorigenesis of LSCC and may serve as a potential target for therapeutic intervention.

Neat1 is a p53-inducible lincRNA essential for transformation suppression

“…Neat1/NEAT1 has been shown previously to control several aspects of cell behavior by enhancing or decreasing cell division, inhibiting cell death, and increasing migration (Chakravarty et al 2014;Chen et al 2015;Choudhry et al 2015;Wu et al 2015;Ma et al 2016;Wang et al 2016). Our findings in the pancreatic cancer model support the notion that Neat1 inhibits cell proliferation.…”

“…In some studies, NEAT1 levels were found to increase during tumorigenesis, and high levels of NEAT1 expression were associated with worse prognosis He et al 2016;Ma et al 2016;Wang et al 2016). NEAT1 can also promote cell survival and/or proliferation of human cancer cell lines, and Neat1 acts as an oncogene in mice subjected to the DMBA-TPA skin carcinogenesis protocol (Adriaens et al 2016).…”

Extracellular vesicle associated long non-coding RNAs functionally enhance cell viability

“…Notably, some of the previously observed cancer-exosome associated lncRNAs BCYRN1(Hu and Lu, 2015), MALAT1 (Gutschner et al, 2013), GAS5 (Smith and Steitz, 1998; Mourtada-Maarabouni et al, 2008; Mourtada-Maarabouni et al, 2009; Kino et al, 2010) and NEAT1(Souquere et al, 2010; Chen et al, 2015; Guo et al, 2015; Y. Li et al, 2015; Pan et al, 2015; Wang et al, 2016) were not observed present above cellular RNAs in the Hela and C33A exosomes assessed here (Figure 1E and Table S3). Interestingly, the top 4 most abundant transcript candidates observed associated with both Hela and C33A exosomes were un-annotated transcripts emanating from genomic deserts that contained DNase hypersensitive regions of high histone acetylation as well as RNAPII and CTCF binding sites.…”

Functional dissection of NEAT1 using genome editing reveals substantial localization of the NEAT1_1 isoform outside paraspeckles

“…Unsurprisingly, there is also a strong link between high NEAT1 expression and more aggressive forms of cancer (Chakravarty et al 2014;Chai et al 2016;Chen et al 2016;Fu et al 2016;Ma et al 2016;Sun et al 2016;Wang et al 2016). In neurological systems, up-regulated expression of NEAT1 has also been observed in the early phase of amyotrophic lateral sclerosis and Huntington's disease, and more interestingly, its expression could also be acutely down-regulated in response to neuronal activity (Nishimoto et al 2013;Sunwoo et al 2016;Barry et al 2017).…”