Objective: The Grainyhead-like (GRHL) genes family were reported to participate in the development of a number of diseases. This study was designed to investigate the role of GRHL  genes family in colon cancer (CC).
Methods: In this study, the transcriptional levels of GRHL  genes family in patients with CC from GEPIA were explored. Meanwhile, the immunohistochemical data of the GRHL  genes family were also obtained in the HPA database. Additionally, we re-identified the mRNA of these genes via real-time PCR. Furthermore, the association between the levels of GRHL  genes and stage plot as well as survival condition including overall survival and disease-free survival of patients with CC was analyzed. Finally, by transfecting with specific-siRNA, clone formation assay was performed to observe the role of GRHL  genes family in the proliferation of SW480 human colon cancer cells.
Results: We found that the mRNA and protein levels of GRHL1 , GRHL2  and GRHL3  were significantly higher in CC tissues than in normal colon tissues. Additionally, GRHL1 , GRHL2  and GRHL3  were significantly associated with the stages of CC. The Kaplan–Meier plotter showed that the low levels of GRHL1 , GRHL2  and GRHL3  conferred a better overall survival of patients with CC while the high levels of GRHL1  and GRHL3  were associated with poor disease-free survival. Knockdown of GRHL1 , GRHL2  and GRHL3  siHgnificantly inhibited the ability of colony formation of human colon cancer cells.
Conclusion: Our study demonstrated that GRHL  genes are involved in the prognosis and survival in patients with CC, the inhibition of which may suppress the proliferation of colon cancer cells.
Keywords: colon cancer, Grainyhead-like genes family, prognosis, biomarkers, bioinformatics