Background: Exosomes play important roles in intercellular communication by delivering microRNAs (miRNAs) that mediate tumor initiation and development, including those in diffuse large B cell lymphoma (DLBCL). To date, however, limited studies on the inhibitory effect of exosomes derived from human bone marrow mesenchymal stem cells (hBMSCs) on DLBCL progression have been reported. Therefore, this study aimed to investigate the role of hBMSC exosomes carrying microRNA-124-3p in the development of DLBCL. Methods: Microarray-based expression analysis was adopted to identify differentially expressed genes and regulatory miRNAs, which revealed the candidate NFATc1. Next, the binding affinity between miR-124-3p and NFATc1 was detected by luciferase activity assays. The mechanism underlying NFATc1 regulation was investigated using lentiviral transfections. Subsequently, DLBCL cells were cocultured with exosomes derived from hBMSCs transfected with a miR-124-3p mimic or control. Proliferation and apoptosis were measured in vitro. Finally, the effects of hBMSC-miR-124-3p on tumor growth were investigated in vivo. Results: MiR-124-3p was expressed at low levels, while NFATc1 was highly expressed in DLBCL cells. MiR-124-3p specifically targeted and negatively regulated the expression of NFATc1 in DLBCL cells, upregulated miR-124-3p-inhibited DLBCL cell proliferation and promoted apoptosis. The miR-124-3p derived from hBMSCs inhibits tumor growth both in vivo and in vitro via downregulation of the NFATc1/cMYC pathway. Conclusion: Human bone marrow-derived mesenchymal stem cell overexpressing microRNA-124-3p represses the development of DLBCL through the downregulation of NFATc1.

Background: Exosomes play important roles in intercellular communication by delivering microRNAs (miRNAs) that mediate tumor initiation and development, including those in diffuse large B cell lymphoma (DLBCL). To date, however, limited studies on the inhibitory effect of exosomes derived from human bone marrow-derived mesenchymal stem cells (hBMSCs) on DLBCL progression have been reported. Therefore, this study aimed to investigate the role of hBMSC-secreted exosomes carrying microRNA-124-3p in the development of DLBCL.Methods: Microarray-based expression analysis was adopted to identify differentially expressed genes and regulatory miRNAs, which revealed the candidate NFATc1. Next, the binding affinity between miR-124-3p and NFATc1 was using luciferase activity assays. The mechanism underlying NFATc1 regulation was investigated using lentiviral transfections. Subsequently, DLBCL cells were cocultured with exosomes derived from hBMSCs transfected with a miR-124-3p mimic or control. Proliferation and apoptosis were measured in vitro. Finally, the effects of hBMSC-derived miR-124-3p on tumor growth were investigated in vivo.Results: MiR-124-3p was downregulated while NFATc1 was upregulated in DLBCL cells. MiR-124-3p specifically targeted and negatively regulated the expression of NFATc1 in DLBCL cells, upregulated miR-124-3p-inhibited DLBCL cell proliferation and promoted apoptosis. In addition, we found that hBMSC-derived exosomes carrying miR-124-3p repressed DLBCL cell proliferation both in vitro and in vivo.Conclusion: hBMSC-derived exosomal miR-124-3p represses the development of DLBCL through the downregulation of NFATc1.

Succinylation has been shown to promote lung cancer development, but its mechanism remains incompletely understood. KAT2A, a succinyltransferase, acts as an oncogene in multiple cancers, but its role in mediating lung cancer progression is unclear. This study aimed to investigate the mechanism by which KAT2A regulates lung cancer progression via succinylation. KAT2A expression was analyzed using UALCAN, GEPIA, and Kaplan–Meier Plotter databases, and validated in lung cancer cell lines and patient‐derived tissues. Quantitative real‐time PCR, Cell Counting Kit‐8 (CCK‐8), EdU staining, and flow cytometry were performed to assess KAT2A's role in lung cancer cell proliferation and apoptosis. KAT2A's target proteins were predicted using LinkedOmics and STRING databases. Additionally, in vivo xenograft models were established to evaluate the effect of KAT2A knockdown on tumor growth. Results indicated that KAT2A expression was significantly elevated in lung cancer cells and tissues and was associated with poor prognosis. KAT2A knockdown inhibited proliferation and promoted apoptosis in lung cancer cells, whereas MYC overexpression reversed these effects. Mechanistically, KAT2A knockdown downregulated MYC by reducing succinylation at K370 and K386 residues. Mutation of these sites abrogated the proliferative effect of MYC overexpression and restored apoptotic activity. Furthermore, in vivo experiments demonstrated that KAT2A knockdown inhibited tumor growth and reduced MYC succinylation. Our findings demonstrate that KAT2A functions as an oncogene in lung cancer by enhancing MYC succinylation. This study identifies KAT2A as a promising therapeutic target for lung cancer.

SQSTM1/p62 is a multifunctional selective autophagy receptor and stress-responsive scaffold protein that integrates autophagy, oxidative stress responses, inflammation, and metabolic signaling. Initially characterized as an autophagic adaptor for ubiquitinated cargo, SQSTM1/p62 is now recognized as a central signaling hub that shapes tumor initiation, progression, metastasis, and therapeutic resistance. Its diverse biological activities arise from a modular domain architecture, dynamic post-translational modifications, and context-dependent interactions with key regulators including LC3, KEAP1, TRAF6, and mTORC1-associated components. In cancer, SQSTM1/p62 can exert both tumor-suppressive and tumor-promoting effects, depending on the cellular lineage, stage of tumorigenesis, autophagic competence, subcellular localization, and microenvironmental context. In this review, we summarize the structural basis of SQSTM1/p62 function, the multilayered mechanisms regulating its expression and activity, and the major signaling pathways organized by SQSTM1/p62 in tumor cells and the tumor microenvironment. We further discuss recent progress in pharmacological targeting of SQSTM1/p62 and highlight the challenges of selectively inhibiting oncogenic SQSTM1/p62 signaling without disrupting its essential physiological functions. Collectively, this review positions SQSTM1/p62 as a context-dependent molecular integrator and a promising, yet complex, therapeutic target in cancer.