Genome-wide Profiling of SOX2 Binding Sites in Small Cell Lung Cancer Reveals Therapeutic Regulatory Networks

Small cell lung cancer (SCLC) is a highly aggressive cancer with a poor prognosis, partly due to the involvement of the transcription factor SOX2, which modulates gene expression linked to oncogenesis and stem cell properties. This study aimed to identify and map SOX2 genomic binding sites in SCLC cell lines H29 and H82 using Chromatin Immunoprecipitation sequencing (ChIP-Seq) to deepen our understanding of its regulatory functions and explore its potential as a therapeutic target. Analysis revealed enriched binding regions on chromosomes 1, 4, 5, 6, 12, and 16. Particularly noteworthy is the overlap of SOX2 binding sites with genes such as ESR1, CPE, BASP1, TUBB2A, TUBB2B, TUBA1A, TUBA1B, and TUBB3. This overlap suggests SOX2’s role in regulating these genes, which are implicated in critical SCLC pathways. Here, ESR1, known for its involvement in cell proliferation and hormone response, indicates that SOX2 might regulate oncogenic pathways that affect tumor growth and treatment responsiveness. These findings underscore SOX2’s complex role across SCLC subtypes and highlight its potential as a therapeutic target, offering a foundation for developing therapies aimed at disrupting SOX2-driven oncogenic mechanisms in SCLC such as gene Silencing techniques, SOX2 inhibitors and epigenetic modulators.