Proteomics reveals the regulation of lentivirus-mediated THBS1 overexpression in ALG1 and its mechanism in meibomian gland carcinoma

ABSTRACT: Meibomian gland carcinoma (MGC) is an aggressive and poorly prognostic eyelid malignancy. Previous studies have demonstrated that miR-3907 is highly expressed in MGC, accelerating tumor progression by negatively regulating THBS1. This study delves into the downstream regulatory mechanisms of THBS1. Using 4D-label-free proteomics, ALG1 was identified as the downstream protein with the highest differential expression and consistent sequencing results following lentivirus-mediated THBS1 overexpression. First, protein-protein docking models predicted that THBS1 interacted with ALG1 through hydrogen bonds formed by key amino acid residues such as ASN-991 and MET-58, creating a stable docking structure. Immunofluorescence and co-immunoprecipitation assays further confirmed the co-localization and interaction between THBS1 and ALG1. In MGC cells, the mRNA expression of ALG1 was notably higher than that in normal meibomian gland cells. Functional assays demonstrated that knockdown of ALG1 evidently inhibited cell malignant properties. Additionally, ALG1 knockdown modulated the expression of epithelial-mesenchymal transition-related genes, which are key modulators of tumor metastasis. Conversely, ALG1 overexpression produced the opposite effects. Therefore, ALG1, as part of the miR-3907/THBS1/ALG1 axis, can serve as a biomarker for targeted diagnosis and treatment of MGC. This study provides valuable insights into potential targeted therapies and personalized treatment strategies for MGC.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Eyelid, Skin Of Eyelid

DISEASE(S): Sebaceous Adenocarcinoma

SUBMITTER: Wei Wang  

LAB HEAD: wei wang

PROVIDER: PXD059655 | Pride | 2025-09-29

REPOSITORIES: Pride