Abstract
Mediator complex subunit 19 (MED19), a component of the Mediator complex, has emerged as a potential regulator of cancer progression, although its downstream transcriptional programs remain poorly understood. Here, we investigated the role of MED19 across 20 human cancer cell lines. An siRNA-mediated knockdown (KD) screen identified A549 lung cancer and MCF-7 breast cancer cells as particularly sensitive to MED19 KD, exhibiting markedly reduced cell viability. Flow cytometric analysis revealed that MED19 KD induced G1-phase arrest, suggesting a role in G1/S-phase progression. RNA sequencing followed by differential expression, Gene Ontology (GO), and chromosomal mapping analyses identified amphiregulin (AREG) and cyclin-dependent kinase regulatory subunit 1B (CKS1B) as candidate downstream effectors in A549 and MCF-7 cells, respectively. Knockdown of AREG or CKS1B inhibited cell proliferation and recapitulated the G1-phase arrest induced by MED19 KD. Moreover, ectopic expression of AREG or CKS1B partially rescued the cell-cycle defects caused by MED19 KD. These findings identify MED19 as a context-dependent regulator of cancer cell proliferation and G1/S-phase progression through distinct downstream transcriptional programs in lung and breast cancer cells.