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The HNF1α-regulated lncRNA HNF1A-AS1 reverses the malignancy of hepatocellular carcinoma by enhancing the phosphatase activity of SHP-1

Overview of attention for article published in Molecular Cancer, February 2018
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  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (81st percentile)
  • High Attention Score compared to outputs of the same age and source (84th percentile)

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1 news outlet
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3 X users

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29 Mendeley
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Title
The HNF1α-regulated lncRNA HNF1A-AS1 reverses the malignancy of hepatocellular carcinoma by enhancing the phosphatase activity of SHP-1
Published in
Molecular Cancer, February 2018
DOI 10.1186/s12943-018-0813-1
Pubmed ID
Authors

Chen-Hong Ding, Chuan Yin, Shi-Jie Chen, Liang-Zhi Wen, Kai Ding, Shu-Juan Lei, Jin-Pei Liu, Jian Wang, Kai-xian Chen, Hua-liang Jiang, Xin Zhang, Cheng Luo, Wei-Fen Xie

Abstract

Our previous study has demonstrated that hepatocyte nuclear factor 1α (HNF1α) exerts potent therapeutic effects on hepatocellular carcinoma (HCC). However, the molecular mechanisms by which HNF1α reverses HCC malignancy need to be further elucidated. lncRNA microarray was performed to identify the long noncoding RNAs (lncRNAs) regulated by HNF1α. Chromatin immunoprecipitation and luciferase reporter assays were applied to clarify the mechanism of the transcriptional regulation of HNF1α to HNF1A antisense RNA 1 (HNF1A-AS1). The effect of HNF1A-AS1 on HCC malignancy was evaluated in vitro and in vivo. RNA pulldown, RNA-binding protein immunoprecipitation and the Bio-Layer Interferometry assay were used to validate the interaction of HNF1A-AS1 and Src homology region 2 domain-containing phosphatase 1 (SHP-1). HNF1α regulated the expression of a subset of lncRNAs in HCC cells. Among these lncRNAs, the expression levels of HNF1A-AS1 were notably correlated with HNF1α levels in HCC cells and human HCC tissues. HNF1α activated the transcription of HNF1A-AS1 by directly binding to its promoter region. HNF1A-AS1 inhibited the growth and the metastasis of HCC cells in vitro and in vivo. Moreover, knockdown of HNF1A-AS1 reversed the suppressive effects of HNF1α on the migration and invasion of HCC cells. Importantly, HNF1A-AS1 directly bound to the C-terminal of SHP-1 with a high binding affinity (KD = 59.57 ± 14.29 nM) and increased the phosphatase activity of SHP-1. Inhibition of SHP-1 enzymatic activity substantially reversed the HNF1α- or HNF1A-AS1-induced reduction on the metastatic property of HCC cells. Our data revealed that HNF1A-AS1 is a direct transactivation target of HNF1α in HCC cells and involved in the anti-HCC effect of HNF1α. HNF1A-AS1 functions as phosphatase activator through the direct interaction with SHP-1. These findings suggest that regulation of the HNF1α/HNF1A-AS1/SHP-1 axis may have beneficial effects in the treatment of HCC.

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The data shown below were collected from the profiles of 3 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 29 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 29 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 7 24%
Researcher 4 14%
Student > Master 4 14%
Student > Bachelor 2 7%
Professor 1 3%
Other 3 10%
Unknown 8 28%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 9 31%
Agricultural and Biological Sciences 4 14%
Medicine and Dentistry 3 10%
Pharmacology, Toxicology and Pharmaceutical Science 1 3%
Environmental Science 1 3%
Other 4 14%
Unknown 7 24%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 11. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 03 December 2022.
All research outputs
#2,891,330
of 23,257,423 outputs
Outputs from Molecular Cancer
#174
of 1,753 outputs
Outputs of similar age
#61,996
of 331,814 outputs
Outputs of similar age from Molecular Cancer
#9
of 58 outputs
Altmetric has tracked 23,257,423 research outputs across all sources so far. Compared to these this one has done well and is in the 87th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 1,753 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.8. This one has done well, scoring higher than 89% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 331,814 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 81% of its contemporaries.
We're also able to compare this research output to 58 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 84% of its contemporaries.