ArticleJournal of translational medicine2026
SHMT2 inhibition triggers mitochondrial apoptosis to suppress lung adenocarcinoma progression.
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
14 authors.
Funding
Abstract
backgroundMitochondrial dysfunction has been implicated in various cancers, including non-small cell lung cancer (NSCLC). This study aimed to elucidate the role of mitochondrial dysfunction in NSCLC prognosis and the molecular mechanisms involved, particularly focusing on the Serine hydroxymethyltransferase 2 (SHMT2), a key enzyme in mitochondrial metabolism.
methodsWe analyzed the expression of SHMT2 in NSCLC tissue and its prognostic correlation by using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus Series (GSE81809) databases. Further, the CRISPR-Cas9 system was employed to establish SHMT2-knockout lung adenocarcinoma (LUAD) cell lines, assessing its impact on cell proliferation and apoptosis through various in vitro assays and in vivo nude mouse xenograft models. Mitochondrial homeostasis was evaluated by assessing the ROS levels, mitochondrial morphology, and membrane potential. Meanwhile, the SHMT2 inhibitor SHIN1 and the ROS scavenger N-Acetylcysteine (NAC) were employed to validate the underlying mechanism.
resultsThe results revealed that SHMT2 was significantly overexpressed in LUAD tissues and was associated with poor patient prognosis. SHMT2-knockout as well as SHIN1-treatment significantly inhibited the proliferation of LUAD cells and induced ROS-dependent mitochondrial apoptosis. Mechanistically, SHMT2 deficiency could increase the recruitment of BAX to mitochondria, reducing ΔΨm, and release of Cytochrome C (Cyto C) from mitochondria, thereby activating the caspase cascade and initiating intrinsic mitochondrial apoptosis. NAC treatment can reverse the apoptosis and mitochondrial dysfunction induced by SHMT2 knockout. In vivo experiments further confirmed that SHMT2 knockout significantly inhibited tumor growth, whereas ROS scavenging attenuated its antitumor effects.
conclusionsOur findings suggest that SHMT2 is vital for regulating LUAD apoptosis by maintaining mitochondrial ROS homeostasis, and its deficiency triggers apoptosis through the ROS-BAX-Cyto C-Caspase signaling. Targeting SHMT2 could thus offer new clinical insights and be a promising strategy for LUAD treatment.
Indexed as
Identifiers
What Socratic 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 Socratic graph.