The interplay between ATF2 and NEAT1 contributes to lung adenocarcinoma progression

Liu, Jian; Li, Kai; Wang, Rui; Chen, Sisi; Wu, Jie; Li, Xiang; Ning, Qian; Yang, Guolong; Pang, Yamei

doi:10.1186/s12935-020-01697-8

Cited by 15 publications

(9 citation statements)

References 35 publications

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“…Four of the top ten loci in lncRNA according to maxHeight are Neat1, and we further confirmed through the RIP experiment that RBM10 can recruit Neat1. One study showed that Neat1 expression increased in LA tissues, and that ATF2 and Neat1 form a positive feedback loop mediated by miR-26a-5p, coordinately contributing to LA progression [ 38 ]. Zhao et al concluded that downregulation of Neat1 in NSCLC inhibits its growth, migration, and invasion through the miR-204/NUAK1 axis [ 39 ].…”

Section: Discussionmentioning

confidence: 99%

RBM10 regulates alternative splicing of lncRNA Neat1 to inhibit the invasion and metastasis of NSCLC

Cong

et al. 2022

Cancer Cell Int

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Background Non-small cell lung cancer (NSCLC) accounts for more than 85% of the total cases with lung cancer. NSCLC is characterized by easy metastasis, which often spreads to bones, brains and livers. RNA-binding motif protein 10 (RBM10) is an alternative splicing (AS) regulator frequently mutated in NSCLC. We found that there were multiple peak binding sites between RBM10 and long non-coding RNA nuclear enriched abundant transcript 1 (LncRNA Neat1) by crosslinking-immunprecipitation and high-throughput sequencing (Clip-Seq). LncRNA Neat1 plays an indispensable role in promoting cancer in a variety of tumors and produces two splicing variants: Neat1_1 and Neat1_2. This study aims to explore the mechanism of RBM10 and LncRNA Neat1 in invasion and metastasis of NSCLC. Methods Through histological and cytological experiments, we assessed the expression level of RBM10 protein expression. The interaction between RBM10 and Neat1 was evaluated via Clip-Seq and RNA immunoprecipitation assay. The effect of RBM10 on Neat1 and its splicing variants was identified by RT-qPCR. The effect of RBM10 and Neat1 on invasive and metastasis phenotypes of NSCLC was analyzed using transwell invasion assay and scratch test. Additionally, downstream signaling pathway of RBM10 were identified by immunofluorescence and western blot. Results RBM10 exhibited low levels of expression in NSCLC tissues and cells. RBM10 inhibited the invasion and metastasis of NSCLC and recruited Neat1 and Neat1_2. Overexpression of RBM10 simultaneously inhibited Neat1 and Neat1_2, and promoted the expression of Neat1_1. On the other hand, silencing RBM10 promoted Neat1 and Neat1_2, and inhibited the expression of Neat1_1. From this, we concluded that RBM10 regulated AS of Neat1, and the tumor-promoting effect of Neat1 was mainly attributed to Neat1_2. RBM10 had a negative correlation with Neat1_2. In addition, RBM10 upregulated the expression of PTEN and downregulated the phosphorylation of PI3K/AKT/mTOR through Neat1_2, which ultimately inhibited the invasion and metastasis of NSCLC. Conclusion The RBM10 regulated AS of Neat1 to cause the imbalance of Neat1_1 and Neat1_2, and RBM10 suppressed the activation of the PTEN/PI3K/AKT/mTOR signal by downregulating Neat1_2, finally affected the invasion and metastasis of NSCLC.

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Section: Discussionmentioning

confidence: 99%

RBM10 regulates alternative splicing of lncRNA Neat1 to inhibit the invasion and metastasis of NSCLC

Cong

et al. 2022

Cancer Cell Int

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“…Realtime PCR was performed using 2 × RealStar Green Fast Mixture (Genstar, Beijing, China) on a CFX96 RealTime PCR system (Bio-Rad, Hercules, CA, USA) according to the manufacturer's instructions. The relative expression levels were calculated using the 2 −ΔΔCt method as previously described [23]. The primer sequences are listed in Additional file 1: Table S1.…”

Section: Quantitative Realtime Pcr (Qrt-pcr)mentioning

confidence: 99%

An SETD1A/Wnt/β-catenin feedback loop promotes NSCLC development

Wang

Liu

et al. 2021

J Exp Clin Cancer Res

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Background SETD1A, a member of SET1/MLL family H3K4 methyltransferases, is involved in the tumorigenesis of numerous cancers. However, the biological role and mechanism of SETD1A in non-small cell lung cancer (NSCLC) remain to be elucidated. Methods The expression of SETD1A, NEAT1, EZH2, and β-catenin in NSCLC tissues and cell lines was detected by qRT-PCR, immunohistochemistry and western blotting. The regulatory mechanisms were validated by chromatin immunoprecipitation, co-immunoprepitation and luciferase reporter assay. The self-renewal, cisplatin sensitivity and tumorigenesis of NSCLC cells were analyzed using sphere formation, CCK-8, colony formation assays and xenograft tumor models. Results SETD1A expression was significantly increased in NSCLC and its overexpression predicted a poor prognosis of patients with NSCLC. Functional experiments showed that SETD1A positively regulated cancer stem cell property and negatively regulated cisplatin sensitivity in NSCLC cells via the Wnt/β-catenin pathway. Next, we found that SETD1A positively regulated the Wnt/β-catenin pathway via interacting with and stabilizing β-catenin. The SET domain is dispensable for the interaction between SETD1A and β-catenin. Furthermore, we identified that SETD1A bound to the promoters of NEAT1 and EZH2 to activate gene transcription by inducing H3K4me3 enrichment. Rescue experiments showed that SETD1A promoted the Wnt/β-catenin pathway and exerted its oncogenic functions in NSCLC, at least, partly through NEAT1 and EZH2 upregulation. In addition, SETD1A was proven to be a direct target of the Wnt/β-catenin pathway, thus forming a positive feedback loop in NSCLC cells. Conclusion SETD1A and Wnt/β-catenin pathway form a positive feedback loop and coordinately contribute to NSCLC progression.

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“…LncRNA NEAT1 plays a carcinogenic role in various tumors, including gastric cancer, lung cancer, colorectal cancer and liver cancer [ 123 ]. Recent studies have shown that NEAT1, as a ceRNA, can be a new target for HCC therapy.…”

Section: The Potential Of Lncrna Related Cernet As Therapy Target In Hccmentioning

confidence: 99%

The role of ceRNA-mediated diagnosis and therapy in hepatocellular carcinoma

et al. 2021

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Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide due to its high degree of malignancy, high incidence, and low survival rate. However, the underlying mechanisms of hepatocarcinogenesis remain unclear. Long non coding RNA (lncRNA) has been shown as a novel type of RNA. lncRNA by acting as ceRNA can participate in various biological processes of HCC cells, such as tumor cell proliferation, migration, invasion, apoptosis and drug resistance by regulating downstream target gene expression and cancer-related signaling pathways. Meanwhile, lncRNA can predict the efficacy of treatment strategies for HCC and serve as a potential target for the diagnosis and treatment of HCC. Therefore, lncRNA serving as ceRNA may become a vital candidate biomarker for clinical diagnosis and treatment. In this review, the epidemiology of HCC, including morbidity, mortality, regional distribution, risk factors, and current treatment advances, was briefly discussed, and some biological functions of lncRNA in HCC were summarized with emphasis on the molecular mechanism and clinical application of lncRNA-mediated ceRNA regulatory network in HCC. This paper can contribute to the better understanding of the mechanism of the influence of lncRNA-mediated ceRNA networks (ceRNETs) on HCC and provide directions and strategies for future studies.

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The interplay between ATF2 and NEAT1 contributes to lung adenocarcinoma progression

Cited by 15 publications

References 35 publications

RBM10 regulates alternative splicing of lncRNA Neat1 to inhibit the invasion and metastasis of NSCLC

RBM10 regulates alternative splicing of lncRNA Neat1 to inhibit the invasion and metastasis of NSCLC

An SETD1A/Wnt/β-catenin feedback loop promotes NSCLC development

The role of ceRNA-mediated diagnosis and therapy in hepatocellular carcinoma

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