S-adenosylhomocysteine hydrolase-like protein 1 (AHCYL1) inhibits lung cancer tumorigenesis by regulating cell plasticity

MUÑOZ-BERNART, MELINA; BUDNICK, NICOLÁS; CASTRO, ARACELI; MANZI, MALENA; MONGE, MARÍA EUGENIA; PIOLI, JULIETA; DEFRANCHI, SEBASTIÁN; PARRILLA, GUSTAVO; SANTILLI, JUAN PABLO; DAVIES, KEVIN; ESPINOSA, JOAQUÍN M.; KOBAYASHI, KEN; VIGLIANO, CARLOS; PEREZ-CASTRO, CAROLINA

BIOLOGY DIRECT

BIOMED CENTRAL LTD

Año: 2023 vol. 18

1745-6150

Background Lung cancer is one of the most frequently diagnosed cancers characterized by high mortality, metastaticpotential, and recurrence. Deregulated gene expression of lung cancer, likewise in many other solid tumors,accounts for their cell heterogeneity and plasticity. S-adenosylhomocysteine hydrolase-like protein 1 (AHCYL1), alsoknown as Inositol triphosphate (IP(3)) receptor-binding protein released with IP(3) (IRBIT), plays roles in many cellularfunctions, including autophagy and apoptosis but AHCYL1 role in lung cancer is largely unknown.Results Here, we analyzed the expression of AHCYL1 in Non-Small Cell Lung Cancer (NSCLC) cells from RNA-seqpublic data and surgical specimens, which revealed that AHCYL1 expression is downregulated in tumors and inversecorrelated to proliferation marker Ki67 and the stemness signature expression. AHCYL1-silenced NSCLC cells showedenhanced stem-like properties in vitro, which correlated with higher expression levels of stem markers POU5F1 andCD133. Also, the lack of AHCYL1 enhanced tumorigenicity and angiogenesis in mouse xenograft models highlightingstemness features.Conclusions These findings indicate that AHCYL1 is a negative regulator in NSCLC tumorigenesis by modulating celldifferentiation state and highlighting AHCYL1 as a potential prognostic biomarker for lung cancer.