CBX8 is the core component of the PCG family
protein PRC1 complex. It is overexpressed in many solid
tumors and plays an important role in the prognosis and biological behaviors of
tumors such as occurrence, development, invasion, and
metastasis. However, exploration of the role and molecular mechanism of CBX8 in
tumors is still in its infancy. Our study found that the down-regulation of CBX8 expression by RNA interference induced differential expression of several
microRNAs in human
colon cancer cells. The 5 most differentially expressed
miRNA precursors (
pre-miRNA) (hsa-miR-363-3p, hsa-miR-378a-3p, hsa-miR-371b-3p, hsa-miR-361-3p, and hsa-miR-576-3p) share a common motif sequence: ARAAAKUGCMC. We selected miR-378a-3p and further revealed that the negative regulation of
miRNA expression by CBX8 mainly occurs in the processing of
pre-miRNA to mature
miRNA. CBX8 uses its own RNA-binding domain to interact with
pre-miRNA, and is dependent on its own nuclear localization characteristics to limit nucleoplasmic transport of
pre-miRNA. Changing the characteristic sequence of
pre-miRNA or mutating the RNA-binding domain and
nuclear localization signal of CBX8 can effectively weaken the regulation of miR-378a-3p expression by CBX8. However, our experimental results showed that miR-378a-3p inhibited the malignant expression of human
colon cancer cells by targeting PDIA4, resulting in increased activity of caspases-3 and -7. In summary, our study suggests that CBX8 acts as an independent
RNA-binding protein to regulate
miRNA expression. Simultaneously, this study shows the correlation between the CBX8/miR-378a-3p/PDIA4 pathway and the malignant biological properties of
colorectal cancer, suggesting this proposed pathway as a possible therapeutic target for human
cancers.