Background:
Colorectal cancer (CRC) is the second leading cause of death
worldwide, and distant metastasis is responsible for the poor prognosis in patients with
advanced-stage CRC. RPS24 (ribosomal protein S24) as a ribosomal protein, multiple
transcript variant encoding different isoforms have been found for this gene. Our
previous studies have demonstrated that RPS24 is overexpressed in CRC. However,
the mechanisms underlying the role of RPS24 in tumor development have not been fully
defined.
Methods:
Expression of RPS24 isoforms and lncRNA MVIH in CRC tissues and cell
lines were quantified by real-time PCR or western blotting assay. Endothelial tube
formation assay was performed to determine the effect of RPS24 on tumor
angiogenesis. The cell viability of HUVEC was determined by MTT assay, and the
migration and invasion ability of HUVEC were detected by transwell assay. PGK1
secretion was tested with a specific ELISA kit.
Results:
Here, we found that RPS24c isoform was a major contributor to tumor
angiogenesis, a vital process in tumor growth and metastasis. Real-time PCR revealed
that RPS24c isoform was highly expressed in CRC tissues, while other isoforms are
present in both normal and CRC tissues with no statistical difference. Moreover the
change of RPS24 protein level is mainly due to the fluctuation of RPS24c. Furthermore,
we observed that silencing RPS24c could decrease angiogenesis by inhibiting tubule
formation, HUVEC cell proliferation and migration. Additionally, we investigated the
molecular mechanisms and demonstrated that RPS24c mRNA interacted with lncRNA
MVIH, the binding-interaction enhanced the stability of each other, thereby activated
angiogenesis by inhibiting the secretion of PGK1.
Conclusion:
RPS24c facilitates tumor angiogenesis via the RPS24c/MVIH/PGK1
pathway in CRC. RPS24c inhibition may be a novel option for anti-vascular treatment in
CRC.
Chitinase 3-like 1 secreted from cancer-associated fibroblasts promotes tumor angiogenesis via interleukin-8 secretion in colorectal cancer