Evidence map›Paper›PMID 41827746›Full record

ArticleCancers2026

Transcriptional Control of Hepatocellular Carcinoma Cells Aggressiveness by AAV2/8-Mediated Delivery of Human Centenarian-Associated SIRT6 N308K/A313S.

Maanya Vittal, Niccolo Liorni, Ahmed Kazaili, Eric Leire, Riaz Akhtar, Tommaso Mazza, Manlio Vinciguerra

Abstract read
In one paragraph

Article in Cancers, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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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

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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

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No citing paper in PubMed yet.

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

7 authors.

Maanya VittalSchool of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool L3 3AF, UK.
Niccolo LiorniComputational Biology and Bioinformatics Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00136 Roma, Italy.ORCID 0000-0003-0472-5693
Ahmed KazailiDepartment of Materials, Design and Manufacturing Engineering, School of Engineering, University of Liverpool, Liverpool L69 3GH, UK.ORCID 0000-0002-0400-7432
Eric LeireGenFlow Biosciences SRL Biopark Gosselies, 10B-6041 Charleroi, Belgium.
Riaz AkhtarDepartment of Materials, Design and Manufacturing Engineering, School of Engineering, University of Liverpool, Liverpool L69 3GH, UK.ORCID 0000-0002-7963-6874
Tommaso MazzaComputational Biology and Bioinformatics Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00136 Roma, Italy.ORCID 0000-0003-0434-8533
Manlio VinciguerraDepartment of Translational Stem Cell Biology, Research Institute, Medical University Varna, 9002 Varna, Bulgaria.

Funding

Horizon 2020 Project 856871-TRANSTEM
6 · The paper itself

Abstract

BACKGROUND/

objectivesHepatocellular carcinoma (HCC) is the sixth most prevalent cancer and a chief cause of cancer-related mortality throughout the world. SIRT6 is a fundamental sirtuin that governs several disease processes encompassing inflammation and cancer, including HCC. Longevity in centenarian Ashkenazi Jews was recently associated to novel allelic variants of SIRT6 (N308K/A313S), which ameliorate genome maintenance and DNA repair, and suppress cancer cells. It is currently unknown whether the above-mentioned SIRT6 variants display divergent or similar roles in HCC pathogenesis, compared to the wild-type (WT) counterpart.

methodsOur goal was to elucidate how these new centenarian-associated SIRT6 genetic variants may modulate HCC cell lines' (HepG2 and Huh-7) aggressiveness and behavior, using functional and transcriptomic approaches.

resultsWe demonstrate that adeno-associated virus (AAV2/8)-mediated overexpression of centenarian-associated SIRT6 variants hampered HCC cell proliferation, with transcriptomic data showing the modulation of hallmark genes involved in the turnover of collagen/extracellular matrix (ECM). In addition, we found that AAV2/8-mediated overexpression of SIRT6 N308K/A313S decreased invasion and also increased stiffness in HCC cells, as measured by nanoindentation, in a more pronounced fashion compared to SIRT6 WT. Intracellular stiffness is a property of the cancer cells themselves, which, along with ECM invasiveness, plays a significant role in the progression of HCC.

conclusionsThese data suggest that increased intracellular stiffening mirrors increased cell motility and invasive behavior; it can be indicative of suppressed cancer development and progression by the centenarian-associated SIRT6 N308K/A313S mutant.

Indexed as

extracellular matrixhepatocellular carcinomaSIRT6stiffnesstranscriptomics

Identifiers

PMID41827746
PMCPMC12984413

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