Knockdown of GRHL2 inhibited proliferation and induced apoptosis of colorectal cancer by suppressing the PI3K/Akt pathway.

Grainyhead-like 2 (GRHL2) transcription factor is implicated in many types of cancers. However, the role of GRHL2 in colorectal cancer (CRC) has not been fully understood. The present study aimed to evaluate the expression and functional roles of GRHL2 in CRC. The expression of GRHL2 in normal human intestinal epithelial cells and colorectal cancer cells was measured by qRT-PCR and western blot. For knockdown of GRHL2, two small interfere RNAs (siRNAs) targeting GRHL2 or control siRNA was transfected into CRC cell lines (HCT116 and HT29). For GRHL2 overexpression, the GRHL2-overexpressing vector or empty lentiviral vector was infected into HCT116 and HT29 cells. Cell proliferation was measured by MTT assay. Cell apoptosis rate was analyzed by flow cytometry. The expression of proliferating cell nuclear antigen (PCNA), Bax, and Bcl-2 was detected by western blot. We found that GRHL2 was upregulated in CRC cells compared to normal human intestinal epithelial cells. Knockdown of GRHL2 inactivated the PI3K/Akt pathway in HCT116 and HT29 cells. Knockdown of GRHL2 inhibited cell viability, elevated the apoptosis rates, suppressed the expression of PCNA and Bcl-2, and induced the expression of Bax in HCT116 and HT29 cells, and these effects were reversed by activation of the PI3K/Akt pathway. Inhibition of PI3K/Akt pathway blocked the effects of GRHL2 overexpression on cell proliferation and apoptosis. In conclusion, GRHL2 acted as an oncoprotein through regulating cell proliferation and apoptosis in CRC cells. The PI3K/Akt pathway was closely involved in the effects of GRHL2. Therefore, GRHL2 might be a therapeutic target for the CRC treatment.

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