Dual roles of LMO2 in promoting tumor angiogenesis and progression

This is the authors' abstract. We don't add key points for this paper.

LIM domain only 2 (LMO2) is a critical transcription factor involved in developmental and adult angiogenesis; however, the specific mechanisms through which LMO2 regulates tumor angiogenesis remain unclear. To comprehensively and systematically explore the transcriptional regulation of LMO2 in tumor angiogenesis, we conducted LMO2 chromatin immunoprecipitation sequencing (ChIP-Seq) in HUVECs and RNA sequencing (RNA-Seq) in LMO2 knockdown (KD) and control HUVECs using small interfering RNA (siRNA). For in vivo siRNA delivery, we screened a highly efficient lipid nanoparticle (LNP) formulation. Mouse models were used to investigate the role of LMO2 in tumor angiogenesis, progression, and metastasis. ChIP-Seq analysis revealed that the binding motifs of LMO2 exhibited a significant overlap with transcription factors from the ETS family. Functional enrichment analysis demonstrated that the genes bound and activated by LMO2 were highly enriched in pathways associated with angiogenesis and cancer. Further analysis of a large breast cancer cohort from the TCGA database and lung cancer data from clinical, along with LMO2 immunohistochemistry scores of human breast cancer tissue chips, revealed a strong correlation between LMO2 expression and cancer progression and metastasis. Moreover, siRNA knockdown of LMO2 in 4T1 and LLC cells impaired their proliferation and migration in vitro . Consistently, LMO2 knockdown in lung and breast cancer mouse models strongly inhibited tumor angiogenesis, progression, and metastasis. Our findings elucidate the transcriptional regulatory landscape of LMO2 in tumor angiogenesis and different cancers. LMO2 emerges as a critical transcription factor governing tumor angiogenesis, cancer progression, and metastasis.