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Laminin subunit alpha-3 (LAMA3) is a critical structural component of the extracellular matrix, specifically forming the alpha chain of the heterotrimeric Laminin-332 molecule [UniProt: P35908]. It plays a fundamental role in maintaining the structural integrity of the dermo-epidermal junction by facilitating the assembly of hemidesmosomes, which anchor epithelial cells to the underlying basement membrane [NCBI Gene: 3909]. Mutations in the LAMA3 gene are a primary cause of Junctional Epidermolysis Bullosa (JEB), a severe genetic disorder characterized by fragile skin and chronic blistering [PMID: 28103471]. In oncology, LAMA3 is frequently overexpressed in various solid tumors, such as squamous cell carcinoma, where it promotes cell migration, invasion, and the epithelial-mesenchymal transition [PMID: 30232345]. Current therapeutic efforts include gene replacement strategies using viral vectors to treat JEB and targeted downregulation via RNA interference for metastatic cancers [PMID: 25600105].
Gene replacement therapy to restore functional protein expression in genetic deficiency; RNA interference or antisense oligonucleotides to downregulate expression in oncogenic contexts [PMID: 25600105, PMID: 28103471].
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