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Hepatocyte-Specific Knock-Out of Nfib Aggravates Hepatocellular Tumorigenesis via Enhancing Urea Cycle

Overview of attention for article published in Frontiers in Molecular Biosciences, May 2022
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Title
Hepatocyte-Specific Knock-Out of Nfib Aggravates Hepatocellular Tumorigenesis via Enhancing Urea Cycle
Published in
Frontiers in Molecular Biosciences, May 2022
DOI 10.3389/fmolb.2022.875324
Pubmed ID
Authors

Li Zhou, Qing-Liang Wang, Lin-Hong Mao, Si-Yuan Chen, Zi-Han Yang, Xue Liu, Yu-Hua Gao, Xiao-Qin Li, Zhi-Hang Zhou, Song He

Abstract

Nuclear Factor I B (NFIB) has been reported to promote tumor growth, metastasis, and liver regeneration, but its mechanism in liver cancer is not fully elucidated. The present study aims to reveal the role of NFIB in hepatocellular carcinogenesis. In our study, we constructed hepatocyte-specific NFIB gene knockout mice with CRISPR/Cas9 technology (Nfib-/-; Alb-cre), and induced liver cancer mouse model by intraperitoneal injection of DEN/CCl4. First, we found that Nfib-/- mice developed more tumor nodules and had heavier livers than wild-type mice. H&E staining indicated that the liver histological severity of Nfib-/- group was more serious than that of WT group. Then we found that the differentially expressed genes in the tumor tissue between Nfib-/- mice and wild type mice were enriched in urea cycle. Furthermore, ASS1 and CPS1, the core enzymes of the urea cycle, were significantly upregulated in Nfib-/- tumors. Subsequently, we validated that the expression of ASS1 and CPS1 increased after knockdown of NFIB by lentivirus in normal hepatocytes and also promoted cell proliferation in vitro. In addition, ChIP assay confirmed that NFIB can bind with promoter region of both ASS1 and CPS1 gene. Our study reveals for the first time that hepatocyte-specific knock-out of Nfib aggravates hepatocellular tumor development by enhancing the urea cycle.

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Mendeley readers

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Geographical breakdown

Country Count As %
Unknown 3 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 1 33%
Unknown 2 67%
Readers by discipline Count As %
Medicine and Dentistry 1 33%
Unknown 2 67%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. 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 June 2022.
All research outputs
#18,810,584
of 23,312,088 outputs
Outputs from Frontiers in Molecular Biosciences
#2,054
of 4,003 outputs
Outputs of similar age
#314,704
of 441,851 outputs
Outputs of similar age from Frontiers in Molecular Biosciences
#183
of 383 outputs
Altmetric has tracked 23,312,088 research outputs across all sources so far. This one is in the 11th percentile – i.e., 11% of other outputs scored the same or lower than it.
So far Altmetric has tracked 4,003 research outputs from this source. They receive a mean Attention Score of 3.3. This one is in the 33rd percentile – i.e., 33% of its peers scored the same or lower than it.
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 441,851 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 18th percentile – i.e., 18% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 383 others from the same source and published within six weeks on either side of this one. This one is in the 38th percentile – i.e., 38% of its contemporaries scored the same or lower than it.