Experiment of HNF4A as a Tumor Suppressor Gene Inhibiting Progression of Colorectal Cancer

Objective To investigate the role of HNF4A in the progression of colorectal cancer.

Methods We constructed colorectal cancer cell lines with HNF4A overexpression or knockdown. The expression level of HNF4A was detected by real-time quantitative PCR and Western blot; the colony forming ability of the cell lines were tested by soft agar and plate clone formation experiments, and the cell proliferation ability were checked by CCK-8 method; the expression levels of stem cell markers were detected by Western blot. The cell migration and invasion abilities were detected by Transwell migration and invasion experiments. The correlation between HNF4A and matrix metalloproteinases MMP2, MMP9 expression in colorectal cancer was analyzed by R2 gene platform and further verified by Western blot.

Results The overexpression of HNF4A inhibited the proliferation, colony formation, migration and invasion of colorectal tumor cells. The knockdown of HNF4A promoted the proliferation, colony formation, migration and invasion of colorectal cancer cells. HNF4A inhibited the expression of colorectal cancer stem cells markers, such as CD133, CD44 and EpCAM, as well as the expression of MMP2 and MMP9. Moreover, the same conclusion was obtained in HNF4A-knockdown cell lines.

Conclusion HNF4A inhibits the progression of colorectal cancer by inhibiting the stem-like cell characteristic and the expression of metalloproteinases.