NEAT1 upregulates TGF‐β1 to induce hepatocellular carcinoma progression by sponging hsa‐mir‐139‐5p

Tu, Jianfei; Zhao, Zhongwei; Xu, Min; Lu, Xiao‐Jie; Liu, Chang; Ji, Jiansong

doi:10.1002/jcp.26524

Cited by 55 publications

(40 citation statements)

References 38 publications

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“…Among the transcripts in RIP-seq results of the IL-6 group, we noticed peroxiredoxin-5 (PRDX5) which may be involved in regulating STAT3 activation. 37 We found that ectopic overexpression of PRDX5 suppressed IL-6-induced STAT3 phosphorylation (Figure5A). IL-6 stimulation increased the association between NONO and PRDX5 mRNA ( Figure 5B), which was decreased by NEAT1_2 knockdown ( Figure 5C), further confirming that PRDX5 mRNA was a paraspeckle-associated RNA.…”

Section: Paraspeckle Promotes Il-6/stat3 Signaling Through Trapping Pmentioning

confidence: 83%

NEAT1 paraspeckle promotes human hepatocellular carcinoma progression by strengthening IL-6/STAT3 signaling

et al. 2018

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The formation of paraspeckle, a stress-induced nuclear body, increases in response to viral infection or proinflammatory stimuli. Paraspeckle consists of lncRNA (nuclear paraspeckle assembly transcript 1, NEAT1) and protein components including NONO, SFPQ, PSPC1, etc., which are shown to be involved in viral infection and cancer. Both NEAT1 and NONO expression increase in human hepatocellular carcinoma (HCC) samples according to TCGA data. However, the role of paraspeckle in HCC progression needs further identification. IL-6 signaling is well known to contribute to HCC progression. Here we reported that IL-6 signaling increased paraspeckle formation in HCC cells. Destruction of paraspeckle formation by silencing the paraspeckle essential components NEAT1_2 or NONO could suppress IL-6induced STAT3 phosphorylation in HCC cells, and consequently repressed IL-6-promoted in vitro HCC cell invasion, cell cycle progression and survival. Mechanistically, paraspeckle promotes IL-6-induced STAT3 phosphorylation by binding and trapping peroxiredoxin-5 (PRDX5) mRNA in nucleus, decreasing protein level of PRDX5 which can directly interact with STAT3 and inhibit STAT3 phosphorylation. Besides, glutathione S-transferase P (GSTP1) protein, which inhibits DNA damage and apoptosis through its detoxification and anti-oxidation function, was also trapped within paraspeckles under IL-6 stimulation. Paraspeckle-trapping of both PRDX5 mRNA and GSTP1 protein contributes to IL-6-increased DNA damage in HCC cells. Our results demonstrate that paraspeckle can nuclear entrap the inhibitors of IL-6/ STAT3 signaling as well as DNA damage, and then strengthen the promoting effect on HCC progression by IL-6. Therefore, paraspeckle contributes to the inflammation-related HCC progression and might be a potential therapeutic target for HCC.

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Section: Paraspeckle Promotes Il-6/stat3 Signaling Through Trapping Pmentioning

confidence: 83%

NEAT1 paraspeckle promotes human hepatocellular carcinoma progression by strengthening IL-6/STAT3 signaling

et al. 2018

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“…MiRNAs are also identified as a regulator in a wide range of biological processes and are reported to interact with lncRNA, forming a regulatory network at post-transcriptional level [9,10]. LncRNA nuclear paraspeckle assembly transcript TTC TCT AGT GTT CCT CAT GGC TCC TGC AAT GCT AGG ACT C STAT3 CGC ACT TTA GAT TCA TTG ATG C AGG TGA GGG ACT CAA ACT G TULP3 AGC CAA CTA CCT TAT CTC CA AGG TTG GAT CTA AGC TTG C miR-770-5p GUA CCA CGU GUC AGG GC CTC TAC AGC TAT ATT GCC AGC CAC miR-4739 GGG AGG AGA GGC GGA G CTC TAC AGC TAT ATT GCC AGC CAC miR-4688 GGC AGC AGA GGA CCU GG CTC TAC AGC TAT ATT GCC AGC CAC GAPDH GAA GGT GAA GGT CGG AGT C GAA GAT GGT GAT GGG ATT TC U6 ATT GGA ACG ATA CAG AGA AGA TT GGA ACG CTT CAC GAA TTT G 1 (NEAT1) was reported as an oncogene in breast cancer [11], osteosarcoma [12] and hepatocellular carcinoma [13].…”

Section: Introductionmentioning

confidence: 99%

STAT3-induced up-regulation of lncRNA NEAT1 as a ceRNA facilitates abdominal aortic aneurysm formation by elevating TULP3

et al. 2020

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Long noncoding RNAs (lncRNAs) were viewed as crucial participants in the pathogenesis of abdominal aortic aneurysm (AAA). LncRNA NEAT1 was recognized as an oncogenic gene in various diseases. However, its function and mechanism in AAA were not precisely documented. Here, we explored the functional role and molecular mechanism of NEAT1 in AAA. Functionally, the effect of NEAT1 on the proliferation was assessed by CCK-8 and EdU assay, while its impact on the apoptosis was evaluated through caspase-3/9 activity and TUNEL assays. As a result, we found that NEAT1 knockdown enhanced the proliferation and impaired the apoptosis of vascular smooth muscle cells (VSMCs). Reversely, overexpressed NEAT1 exerted anti-proliferation and pro-apoptosis effects in VSMCs. Mechanically, we found that STAT3 acted as a transcription factor and contributed to NEAT1 transcription by ChIP and luciferase reporter assays. In addition, NEAT1 was confirmed as a sponge of miR-4688 and thereby increase the expression of TULP3 in VSMCs via RIP assay and RNA pull-down assay. Rescue experiments indicted that TULP3 overexpressing countervailed the impact of NEAT1 depletion on AAA biological processes. Conclusively, lncRNA NEAT1 induced by STAT3 was identified as a ceRNA and facilitated AAA formation by targeting miR-4688/TULP3 axis.

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“…5 For instance, CRNDE, TUG1 and NEAT1 are three examples of lncRNAs that are often elevated in HCC and are related to worse prognoses. [6][7][8] MicroRNAs (miRNAs) are a family of small noncoding RNAs 9 that post-transcriptionally control mRNAs by binding to their 3ʹ untranslated regions (UTRs) leading to direct transcript degradation or translational repression. 10 It is estimated that miRNAs can modulate more than 70% of human genes.…”

Section: Introductionmentioning

confidence: 99%

<p>LINC02476 Promotes the Malignant Phenotype of Hepatocellular Carcinoma by Sponging miR-497 and Increasing HMGA2 Expression</p>

Duan¹,

Zhao²,

Jiang³

et al. 2020

OTT

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Background: Long noncoding RNAs (lncRNAs) can promote hepatocellular carcinoma (HCC) initiation and progression. In this report, we examined the role of lncRNA LINC02476 in HCC. Methods: The expression levels of different lncRNAs in HCC were explored using the TCGA database and lncRNA LINC02476 was selected for further study. The expression of LINC02476 in HCC tissues was determined by real-time PCR. The clinicopathological characteristics of HCC patients were analyzed relative to the expression of LINC02476. The expression of LINC02476 was downregulated in HCC cells using a lentiviral vector and different assays were performed to study cell growth, proliferation, invasion, apoptosis and the cell cycle. MiR-497 was selected as a miRNA that could interact with LINC02476 which was further tested by RNA immunoprecipitation. HMGA2 was selected as a possible target of miR-497, and their interaction was examined by a luciferase reporter assay. Results: LINC02476 expression was elevated in HCC cell lines and HCC tissues. When LINC02476 was downregulated, the growth and the invasion of HCC cells decreased in vitro and in vivo. LINC02476 negatively regulated the expression of miR-497 by acting as a ceRNA. HMGA2 was directly targeted and inhibited by miR-497. Conclusion: The results indicate that LINC02476 functions through the miR-497/HMGA2 axis and that it has a role in the growth and metastasis of HCC cells. Therefore, LINC02476 could be an interesting new molecular target in HCC therapies.

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NEAT1 upregulates TGF‐β1 to induce hepatocellular carcinoma progression by sponging hsa‐mir‐139‐5p

Cited by 55 publications

References 38 publications

NEAT1 paraspeckle promotes human hepatocellular carcinoma progression by strengthening IL-6/STAT3 signaling

NEAT1 paraspeckle promotes human hepatocellular carcinoma progression by strengthening IL-6/STAT3 signaling

STAT3-induced up-regulation of lncRNA NEAT1 as a ceRNA facilitates abdominal aortic aneurysm formation by elevating TULP3

<p>LINC02476 Promotes the Malignant Phenotype of Hepatocellular Carcinoma by Sponging miR-497 and Increasing HMGA2 Expression</p>

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