LRPPRC promotes the progression of colorectal cancer via HIF-1ꭤ/VEGF-meditated angiogenesis

Distant metastasis is the primary cause of mortality in patients with colorectal cancer (CRC). Angiogenesis plays a critical role in cancer development, invasion, and metastasis. However, the signaling mechanisms driving angiogenesis were not fully elucidated. This study investigated the role of leucine-rich pentatricopeptide repeat motif-containing protein (LRPPRC) in CRC metastasis.

The impact of LRPPRC was assessed in CRC cells and a mouse xenograft model. The correlation between LRPPRC expression level and clinicopathological features was analyzed through immunohistochemical (IHC) staining on CRC tissue microarrays. LRPPRC-induced proliferation and angiogenesis were evaluated using immunoblotting, immunofluorescence, HUVEC-based tube formation, co-immunoprecipitation, and invasion assays. Gain-of-function experiments were performed to assess the function of LRPPRC in cell proliferation and angiogenesis.

LRPPRC expression level was significantly upregulated in CRC tissues, and a higher LRPPRC expression level was associated with a progressive prognosis and poorer survival in CRC patients. The mouse xenograft model indicated that overexpression of LRPPRC significantly promoted CRC development via angiogenesis. Additionally, LRPPRC induced vascular endothelial growth factor (VEGF) expression level, and the restoration of VEGF rescued the angiogenesis suppression caused by LRPPRC knockdown. LRPPRC promoted the activation of hypoxia-inducible factor 1-alpha (HIF-1α) by interacting with it in CRC cells.

It was revealed that LRPPRC effectively promoted CRC growth and angiogenesis by activation of the HIF-1α/VEGF signaling pathway. The findings may provide a new treatment target and a potential prognostic biomarker for CRC development.