c‐Myb promotes growth and metastasis of colorectal cancer through c‐fos‐induced epithelial‐mesenchymal transition

Abstract

c‐Myb is a crucial transcription factor that participates in various biological functions; however, its role in colorectal cancer (CRC) remains poorly investigated. We first analyzed the expression and clinical significance of c‐Myb in a retrospective cohort enrolling 132 CRC patients. Then, the CRISPR/Cas9 technique was used to establish c‐Myb gene KO CRC cell lines. Cellular functional assays in vitro and in vivo were used to evaluate the impact of c‐Myb KO in CRC cells. Finally, RNA sequencing was used to investigate the potential oncogenic mechanisms regulated by c‐Myb in CRC progression and related cellular validations were accordingly carried out. As a result, c‐Myb is significantly overexpressed in CRC tissues as compared with adjacent normal tissues. High expression of c‐Myb is positively correlated with lymph node metastasis and poor prognosis. Univariate analysis and multivariate analysis further identify c‐Myb as an independent unfavorable prognostic factor for CRC patients. c‐Myb KO inhibits the proliferation, apoptosis resistance, invasion, metastasis, colony formation and in vivo tumorigenesis of CRC cells. Also, the mechanism investigation indicates that c‐Myb may promote CRC progression by regulating c‐fos. c‐fos overexpression can rescue the inhibitory effect of c‐Myb KO on the malignant characteristics of CRC cells. Finally, we find that c‐Myb KO inhibits the epithelial‐mesenchymal transition (EMT) molecular phenotype in CRC cells, whereas c‐fos overexpression can rescue this inhibitory effect. This study suggests that c‐Myb promotes the malignant progression of CRC through c‐fos‐induced EMT and has the potential to be a promising prognostic biomarker and therapeutic target.

Identification of prognostic factors for intrahepatic cholangiocarcinoma based on long non-coding RNAs-associated ceRNA network

“…C-terminally truncated FOS mutant has been previously reported to be expressed in epithelioid hemangioma [14]. The expression of FOS has been proposed to be positively related to c-Myb expression in colorectal cancer cells, while c-Myb expression is repressed in colorectal cancer tissues, suggesting that expression of FOS is also downregulated in colorectal cancer tissues [15], which is concordant with the current study. Meanwhile, the elevation of FOS-like antigen 1 expression is positively correlated with progression of perihilar cholangiocarcinoma [16].…”

Identification of prognostic factors for intrahepatic cholangiocarcinoma using long non-coding RNAs-associated ceRNA network

“…FOS proteins are characterized by a leucine zipper motif and a basic region with a helix-turn-helix motif that binds to DNA and serve as an oncogene and as transcription factors by binding on the DNA sequences [23]. The expression of FOS has been proposed to be positively related with the expression of c-Myb in colorectal cancer cells, while the expression of c-Myb is repressed in colorectal cancer tissues, suggesting that expression of FOS is also downregulated in colorectal cancer tissues [24], which is concordant with the current study. The elevation of FOS-like antigen 1 expression is positively correlated with the progression of perihilar cholangiocarcinoma [25].…”

GINS complex subunit 4, a prognostic biomarker and reversely mediated by Krüppel‐like factor 4, promotes the growth of colorectal cancer

“…Colorectal cancer is the third most common tumor and the third leading cause of cancer‐related death in man and women in the world 1,2 . In China, there was an increase of over 376 300 cases of CRC and a total of 191 000 deaths during 2015 3 .…”