Evidence map›Paper›PMID 37511536›Full record

ArticleInternational journal of molecular sciences2023

Let-7a Downregulation Accompanied by KRAS Mutation Is Predictive of Lung Cancer Onset in Cigarette Smoke-Exposed Mice.

Alessandra Pulliero, Luca Mastracci, Letizia Tarantini, Zumama Khalid, Valentina Bollati, Alberto Izzotti

Open access · goldAbstract read
In one paragraph

Article in International journal of molecular sciences, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
2.4field-weighted citation impact, top 11% 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

9 citing papers in PubMed, 10 citations in OpenAlex.

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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

6 authors at 3 institutions in 1 country.

Alessandra PullieroDepartment of Health Sciences, University of Genoa, 16132 Genoa, Italy.ORCID 0000-0001-5378-9517
Luca MastracciDepartment of Surgical Sciences and Integrated Diagnostics (DISC), Anatomic Pathology, University of Genoa, 16132 Genoa, Italy.ORCID 0000-0003-0193-5281
Letizia TarantiniEpiget Lab, Department of Clinical Sciences and Community Health, University of Milan, 20122 Milan, Italy.
Zumama KhalidDepartment of Health Sciences, University of Genoa, 16132 Genoa, Italy.
Valentina BollatiEpiget Lab, Department of Clinical Sciences and Community Health, University of Milan, 20122 Milan, Italy.ORCID 0000-0002-0370-9598
Alberto IzzottiIRCCS Ospedale Policlinico San Martino, 16132 Genova, Italy.ORCID 0000-0002-8588-0347
Ospedale Policlinico San Martino · ITUniversity of Genoa · ITUniversity of Milan · IT

Funding

Italian Association for Cancer Research AIRC, IG2017-20699 to A.I.).
6 · The paper itself

Abstract

backgroundLet-7 is a tumor suppressor microRNA targeting the KRAS lung oncogene. Let-7a downregulation is reversible during the early stages of lung carcinogenesis but is irreversible in cancer cells. The aim of this study is to shed light on the relationship between oncogene (KRAS) mutation and let-7a downregulation in cigarette smoke (CS)-induced lung carcinogenesis.

methodsA total of 184 strain H Swiss albino mice were either unexposed (control) or exposed to CS for 2 weeks (short CS) or 8 months (long CS). After 8 months, the lungs were individually collected. The following end points have been evaluated: (a) DNA methylation of the let-7a gene promoter by bisulphite-PCR and pyrosequencing; (b) let-7a expression by qPCR; (c) KRAS mutation by DNA pyrosequencing; (d) cancer incidence by histopathological examination.

resultslet-7a expression decreased by 8.3% in the mice exposed to CS for two weeks (CS short) and by 33.4% (

conclusionsThe effects of CS-induced mutations in KRAS are neutralized by the high expression of let-7a in cancer-free mice (positive correlation) but not in cancer-bearing mice where an irreversible let-7a downregulation occurs (negative correlation). This result provides evidence that both genetic (high load of KRAS mutation) and epigenetic alterations (let-7a irreversible downregulation) are required to produce lung cancer in CS-exposed organisms.

Indexed as

Cigarette SmokingLung NeoplasmsMicroRNAsAnimalsCarcinogenesisDown-RegulationMiceMutationProto-Oncogene Proteins p21(ras)MicroRNAsProto-Oncogene Proteins p21(ras)cigarette smokeKRAS mutationlet-7a expressionlung cancermicroRNA

Identifiers

PMID37511536
PMCPMC10380304
OpenAlexW4385172693

What OpenQuestion holds

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Registered trials

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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.