DIAPH3 is a prognostic biomarker and inhibit colorectal cancer progression through maintaining EGFR degradation

Abstract

Abstract Background Actin cytoskeleton is connected with the processes of cell proliferation and migration in colorectal cancer (CRC). However, it is unknown how to accomplish these adjustments in CRC by actin cytoskeleton genes (ACGs) and here we investigated the role of hub prognosis‐related ACGs‐Diaphanous‐related formin 3 (DIAPH3) in CRC, as a potential, novel target. Methods The ACGs gene set from the Kyoto Encyclopedia of Genes and Genomes (KEGG) was used to group CRC patients and select prognosis‐related ACGs by univariate and multivariate Cox regression for constructing prognostic model. Next, we tested hub prognosis‐related ACGs‐ DIAPH3 expression in CRC and clarified the role of DIAPH3 by shRNA constructs in KM12 and SW480. Activation of EGFR was analyzed by western blot and immunofluorescence. Results The results showed that actin cytoskeleton function is a significant prognostic factor for CRC patients and related to clinicopathological characteristics such as T stage and lymph node metastasis. A prognostic model constructed by four prognosis‐related ACGs has a moderate intensity to 1‐year Survival (AUC = 0.71). And hub prognosis‐related ACGs DIAPH3 is downregulated in CRC. Knockdown of DIAPH3 could promote the proliferation and migration capacity of CRC. In addition, DIAPH3‐silenced cells increase EGFR phosphorylation by inhibiting EGFR transportation to lysosome. Conclusions ACGs play a significant role in tumor invasion and have the potential to predict the prognosis of CRC. Prognosis‐related ACGs DIAPH3 might be a new prognostic biomarker and DIAPH3 could inhibit CRC progression through maintaining EGFR degradation.

Keywords

• actin cytoskeleton
• colorectal cancer
• DIAPH3
• EGFR
• prognosis