DLEU2 promotes cell motility and immune infiltration in cervical squamous cell carcinoma through reciprocal feed-forward activation of E2F1
Cancer metastasis is the primary cause of high mortality in patients with cervical squamous cell carcinoma (CESC). The invasive ability of cancer cells is enhanced by increased cell motility, which contributes to their distant metastasis. The oncogenic lncRNA DLEU2, implicated in tumor progression and prognosis, remains understudied in CESC. This study investigated how DLEU2 enhances cell motility and regulates immune infiltration in CESC. We found that DLEU2 was upregulated in CESC tissues and correlated with poor prognosis in advanced-stage patients. Functionally, DLEU2 knockdown suppressed cell migration and invasion, while its overexpression enhanced motility. Mechanistically, DLEU2 knockdown altered the expression of downstream genes related to cell motility and adhesion. An interaction between DLEU2 and E2F1 protein was confirmed by RNA pulldown assay. E2F1 expression was downregulated or upregulated after DLEU2 knockdown or overexpression, respectively, while DLEU2 expression was also upregulated after E2F1 overexpression. Therefore, DLEU2 may form a regulatory loop with E2F1 to activate the transcription of downstream genes related to cell motility and adhesion. Additionally, E2F1 expression strongly correlated with immune infiltration levels (e.g., T cells, Tregs, monocytes, mast cells), and DLEU2 exhibited a parallel immune cell abundance pattern,  suggesting indirect immunomodulatory effects via E2F1. These findings propose that the DLEU2-E2F1 axis promotes CESC metastasis by dual mechanisms: enhancing tumor cell motility and reshaping the immune microenvironment. The study highlights DLEU2 as a potential therapeutic target to disrupt metastatic pathways and immune evasion in CESC. Further validation is needed to explore clinical applications of targeting this regulatory network. Overall design: 7 unique pairs of biopsy and surgical resection specimens and 1 pairs of cell lines samples were sequenced and profiled.