Evidence map›Paper›PMID 22698995›Full record

ArticleBiochimica et biophysica acta

The let-7 microRNA enhances heme oxygenase-1 by suppressing Bach1 and attenuates oxidant injury in human hepatocytes.

Weihong Hou, Qing Tian, Nury M Steuerwald, Laura W Schrum, Herbert L Bonkovsky

Open access · greenAbstract read
In one paragraph

Article in Biochimica et biophysica acta. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.

0numbers the graph read from it
0cells of the map it votes in
62citing papers in PubMed
5.2field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

62 citing papers in PubMed, 102 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
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  7. Review
  8. Antioxidants (Basel, Switzerland) · 2022
    Article
  9. Article
  10. Review
  11. Article
  12. Observational
  13. Review
  14. Review
  15. Review
  16. Review
  17. miR-98 reduces endothelial dysfunction by protecting blood-brain barrier (BBB) and improves neurological outcomes in mouse ischemia/reperfusion stroke model.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2020
    Article
  18. Review
  19. Article
  20. [Progress on epigenetic regulation of iron homeostasis].Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2020
    Review

2 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 2 institutions in 1 country.

Weihong HouThe Liver-Biliary-Pancreatic Center, Carolinas Medical Center, Charlotte, NC, USA. weihong.hou@carolinashealthcare.org
Qing Tian
Nury M Steuerwald
Laura W Schrum
Herbert L Bonkovsky
Carolinas Medical Center · USUniversity of North Carolina at Charlotte · US

Funding

REGULATION OF HEPATIC HEME METABOLISMR01DK038825 · NIDDK · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI BONKOVSKY, HERBERT L · 1987 to 2009
$3.4M
NIDDK NIH HHS R01 DK038825NIDDK NIH HHS R01-DK38825
6 · The paper itself

Abstract

The let-7 microRNA (miRNA) plays important roles in human liver development and diseases such as hepatocellular carcinoma, liver fibrosis and hepatitis wherein oxidative stress accelerates the progression of these diseases. To date, the role of the let-7 miRNA family in modulation of heme oxygenase 1 (HMOX1), a key cytoprotective enzyme, remains unknown. Our aims were to determine whether let-7 miRNA directly regulates Bach1, a transcriptional repressor of the HMOX1 gene, and whether indirect up-regulation of HMOX1 by let-7 miRNA attenuates oxidant injury in human hepatocytes. The effects of let-7 miRNA on Bach1 and HMOX1 gene expression in Huh-7 and HepG2 cells were determined by real-time qRT-PCR, Western blot, and luciferase reporter assays. Dual luciferase reporter assays revealed that let-7b, let-7c, or miR-98 significantly decreased Bach1 3'-untranslated region (3'-UTR)-dependent luciferase activity but not mutant Bach1 3'-UTR-dependent luciferase activity, whereas mutant let-7 miRNA containing base complementarity with mutant Bach1 3'-UTR restored its effect on mutant reporter activity. let-7b, let-7c, or miR-98 down-regulated Bach1 protein levels by 50-70%, and subsequently up-regulated HMOX1 gene expression by 3-4 fold, compared with non-specific controls. Furthermore, Huh-7 cells transfected with let-7b, let-7c or miR-98 mimic showed increased resistance against oxidant injury induced by tert-butyl-hydroperoxide (tBuOOH), whereas the protection was abrogated by over-expression of Bach1. In conclusion, let-7 miRNA directly acts on the 3'-UTR of Bach1 and negatively regulates expression of this protein, and thereby up-regulates HMOX1 gene expression. Over-expression of the let-7 miRNA family members may represent a novel approach to protecting human hepatocytes from oxidant injury.

Indexed as

3' Untranslated RegionsBasic-Leucine Zipper Transcription FactorsFanconi Anemia Complementation Group ProteinsGene Expression Regulation, EnzymologicHeme Oxygenase-1HepatocytesHep G2 CellsHumansMicroRNAsMutationOxidative StressReal-Time Polymerase Chain Reactiontert-ButylhydroperoxideUp-Regulation3' Untranslated RegionsBACH1 protein, humanBasic-Leucine Zipper Transcription FactorsFanconi Anemia Complementation Group ProteinsHeme Oxygenase-1HMOX1 protein, humanMicroRNAsMIRN98 microRNA, humanmirnlet7 microRNA, humantert-Butylhydroperoxide

Identifiers

PMID22698995
PMCPMC3480558
OpenAlexW1979021654

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.