ArticleJournal of translational medicine2026
Hypoxia/lactate orchestrates the reprogramming metabolism of lung adenocarcinoma by modulating the SIRT2-mediated acetylation.
Article in Journal of translational medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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.
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.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors.
Funding
Abstract
backgroundSilent information regulator 2 (SIRT2) has been described to have dual roles as an oncogene and tumor suppressor gene in non-small cell lung cancer, but its functional selection and the precise mechanisms of its action remain to be elucidated.
methodslung adenocarcinoma (LUAD) tissue microarrays and cell lines were used to detect SIRT2 expression using Immunohistochemistry and Western blotting. SIRT2 overexpression, knockdown, and knockout LUAD cells were constructed to test SIRT2 function in vitro and in vivo, and targeted metabolomics, proteomics, and acetylation analyses were performed to explore the detailed mechanisms by which SIRT2 affects the biological characteristics of LUAD.
resultsSIRT2 is not only downregulated in LUAD tissues and cells, but also associated with poor prognosis in LUAD patients, not in lung squamous cell carcinoma. We also found that hypoxia-induced increasement in lactate levels led to this decreased SIRT2 expression. Remarkably, SIRT2 deficiency promotes the proliferation and metastasis of LUAD cells in vitro and in vivo, while SIRT2 overexpression exerts the opposite function. Mechanistically, SIRT2 deficiency leaded to increased acetylation levels of multiple enzymes involved in glycolysis, tricarboxylic acid cycle, fatty acid oxidation, and glutaminolysis. And results of co-inmunoprecipitation showed that SIRT2 bound to the above enzymes. Accordingly, SIRT2-deficient LUAD cells showed altered metabolic activities such as glycolysis, pentose phosphate pathway, TCA cycle, serine metabolism, and urea cycle. Notably, SIRT2 deletion increases glycolytic capacity of LUAD cells by increasing the acetylation modification of LDHA at the K118 site.
conclusionThis study reveals that hypoxia-induced lactate elevation decreases SIRT2 expression to promote LUAD progression, with the mechanism related to promoting glycolysis by increasing LDHA acetylation. In addition, decreased SIRT2 expression has also been found to cause alterations in many metabolic pathways with no verification mechanism.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.