Given that
colorectal cancer stem cells (CCSCs) play key roles in the
tumor dormancy,
metastasis, and relapse, targeting CCSCs is a promising strategy in
cancer therapy. Here, we aimed to identify the new regulators of CCSCs and found that
Cullin 4B (CUL4B), which possesses oncogenic properties in multiple solid
tumors, drives the development and
metastasis of
colon cancer by sustaining
cancer stem-like features. Elevated expression of CUL4B was confirmed in colon
tumors and was associated with poor overall survival. Inhibition of CUL4B in
cancer cell lines and patient-derived
tumor organoids led to reduced sphere formation, proliferation and
metastasis capacity. Mechanistically, CUL4B coordinates with PRC2 complex to repress miR34a expression, thus upregulates oncogenes including MYCN and NOTCH1, which are targeted by miR34a. Furthermore, we found that elevated CUL4B expression is associated with miR34a downregulation and upregulation of miR34a target genes in
colon cancer specimens. Collectively, our findings demonstrate that CUL4B functions to repress miR34a in maintaining
cancer stemness in CRC and provides a potential therapeutic target.