The interferon regulatory factor 6 promotes cisplatin sensitivity in colorectal cancer

Abstract

Colorectal cancer (CRC) is one of the most common malignancies and causes of cancer-related mortality worldwide. Cell proliferation and tumor metastasis as well as chemoresistance are correlated with poor survival of CRC. The interferon regulatory factor 6 (IRF6) is functioned as a tumor suppressor gene in several cancers and is associated with risk of CRC. We explored the role of IRF6 in CRC in the present study. The protein expressions of IRF6 in human CRC tissues, normal para-carcinoma tissue and liver metastases from CRC were measured. Cell proliferation, chemotherapeutic sensitivity, cell apoptosis, migration and invasion including the related markers along with IRF6 expression were explored. Our results indicated that IRF6 expression in CRC and liver metastasis were lower than normal tissues, which were correlated positively with E-cadherin and negatively with Ki67 expression in CRC tissue. IRF6 promoted CRC cell sensitivity to cisplatin to suppress cell proliferation, migration and invasion as well as aggravate cell apoptosis. Our study suggested that IRF6 may enhance chemotherapeutic sensitivity of cisplatin mediated by affecting cell proliferation, migration and invasion along with apoptosis through regulating E-cadherin and Ki67, while the identified molecular mechanisms remain to be further explored.

Classification of molecular subtypes for colorectal cancer and development of a prognostic model based on necroptosis-related genes

“…We also predicted patients’ drug sensitivity to chemotherapy and observed that C2 cluster was more sensitive to these common chemotherapy drugs. Cisplatin and Imatinib (STI571) has also been used for CRC treatment [ [45] , [46] , [47] ]. In vitro study, we found that Sunitinib drug eluting beads and Dasatinib could effectively inhibit the growth of human CRC cells [ 48 , 49 ].…”

Oncogenic YAP mediates changes in chromatin accessibility and activity that drive cell cycle gene expression and cell migration

“…We identified a group of enhancer-associated genes regulated by ΔNp63 and YAP5SA, many of which have previously been shown to be involved in cell migration and adhesion. One example is interferon regulatory factor 6 (IRF6) which was strongly downregulated by YAP5SA and which has been shown to inhibit migration and cell invasion in squamous cell carcinomas and colorectal cancer cells ( 78 , 79 ). Further investigation is required to determine whether suppression of IRF6 contributes to YAP-mediated migration.…”

A Comprehensive Analysis of Interferon Regulatory Factor Expression: Correlation with Immune Cell Infiltration and Patient Prognosis in Endometrial Carcinoma

“…IRFs show an imbalance expression and played different roles in the occurrence and development of in many different cancers [24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39]. IRF6 might enhance chemotherapeutic sensitivity of cisplatin in colorectal cancer [36].…”

“…IRFs show an imbalance expression and played different roles in the occurrence and development of in many different cancers [24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39]. IRF6 might enhance chemotherapeutic sensitivity of cisplatin in colorectal cancer [36]. IRF4 was overexpressed and activated the cancer progression by Notch signaling pathway in human non-small-cell lung cancer [37].…”