Published online Sep 21, 2020. doi: 10.3748/wjg.v26.i35.5328
Peer-review started: July 6, 2020
First decision: July 28, 2020
Revised: August 7, 2020
Accepted: August 26, 2020
Article in press: August 26, 2020
Published online: September 21, 2020
Our previous study demonstrated that RBBP4 is upregulated in colon cancer and correlated with poor prognosis of colon cancer and hepatic metastasis. However, the potential biological function of RBBP4 in colon cancer is still unknown.
To explore the potential mechanisms underlying colon cancer development and discover biomarkers for the treatment of colon cancer.
To investigate the underlying mechanisms of RBBP4 in colon cancer malignant development.
Real-time polymerase chain reaction and western blot analysis were used to detect the expression of RBBP4 in colon cancer cell lines. The cell proliferation and viability of SW620 and HCT116 cells with RBBP4 knockdown was detected by Cell Counting Kit-8 and 5-ethynyl-2’-deoxyuridine staining. The transwell assay was used to detect the invasion and migration capabilities of colon cancer cells with RBBP4 knockdown. Flow cytometry apoptosis assay was used to detect the apoptosis of colon cancer cells with RBBP4 knockdown. Western blot analysis was used to detect the expression of epithelial-mesenchymal transition and apoptosis related markers in colon cancer with RBBP4 knockdown. The nuclear translocation of β-catenin was examined by western blot analysis in colon cancer cells with RBBP4 knockdown. The TOPFlash luciferase assay was used to detect effect of RBBP4 on Wnt/β-catenin activation. The rescue experiments were performed in colon cancer cells treated with Wnt/β-catenin activator LiCl and RBBP4 knockdown.
We found that RBBP4 was highly expressed in colon cancer cell lines. The 5-ethynyl-2’-deoxyuridine assay showed that knockdown of RBBP4 significantly inhibited cell proliferation. RBBP4 inhibition reduced cell invasion and migration via regulating proteins related to epithelial-mesenchymal transition. Knockdown of RBBP4 significantly inhibited surviving-mediated apoptosis. Mechanistically, the TOPFlash assay showed that RBBP4 knockdown increased activity of the Wnt/β-catenin pathway. RBBP4 knockdown suppressed nuclear translocation of β-catenin. With a Wnt/β-catenin activator, rescue experiments suggested that the role of RBBP4 in colon cancer progression was dependent on the Wnt/β-catenin pathway.
This study demonstrated that RBBP4 promoted colon cancer development via increasing activity of the Wnt/β-catenin pathway. RBBP4 may serve as a novel therapeutic target in colon cancer.
In the future, additional research will be carried out to further explore the important role of RBBP4 and whether RBBP4 knockdown can be employed to enhance the sensitivity of chemotherapy of colon cancer and to develop novel anticancer treatments.