Transcription factor 7 promotes the progression of perihilar cholangiocarcinoma by inducing the transcription of c-Myc and FOS-like antigen 1

Abstract

Background: Perihilar cholangiocarcinoma (PHCC) is the most common type of cholangiocarcinoma with the worst prognosis. Radical resection of PHCC is difficult; thus, few effective biomarkers or useful molecular profiles for PHCC have been reported in recent years. Therefore, in this study, we aimed to assess biomarkers for PHCC. Methods: We screened potential biomarkers for PHCC using exome and transcriptome sequencing with PHCC tissues and paired normal tissues. Transcription factor 7 (TCF7) expression was evaluated using quantitative reverse transcription polymerase chain reaction, western blotting, and immunohistochemistry. The correlations between TCF7 and clinicopathological factors were analyzed with Chi-square test, and the prognostic significance of TCF7 was evaluated with univariate and multivariate analyses. The functions of TCF7 and its main effectors in PHCC cells were investigated in vitro and in vivo. Findings: TCF7 expression was upregulated in PHCC and was an unfavorable prognostic biomarker. c-Myc was a main effector of TCF7 in PHCC cells and modulated TCF7-induced proliferation, invasion, and migration. FOS-like antigen 1 (FOSL1) was identified as a downstream target of TCF7 and was required in TCF7-induced PHCC proliferation. Triple-positive expression of TCF7, c-Myc, and FOSL1 predicted a much worse prognosis in patients with PHCC than TCF7 expression alone. Interpretation: Postoperative detection of TCF7, c-Myc, and FOSL1 may be useful for stratifying patients with a high risk of unfavorable prognosis, and suppressing TCF7 or its downstream effectors may be a promising strategy for the treatment of PHCC.

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

“…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 ]. More importantly, a prior research illustrated that FOS was involved in gene expression regulated by TGF-β [ 26 ].…”

<p>Bone Marrow Stromal Antigen 2 is a Potential Unfavorable Prognostic Factor for High-Grade Glioma</p>

“…To detect BST2 protein expression in sample tissues, IHC examination was conducted as described previously. 16 Briefly, deparaffinized and rehydrated slides were treated with 10 mM citrate buffer (pH 6.0) at 95°C for antigen recovery, followed by quenching the endogenous peroxidase activity with 3% H 2 O 2 incubation. 5% Fetal bovine serum (FBS) was then used to block the nonspecific binding sites.…”

LncRNA MNX1-AS1 promotes progression of intrahepatic cholangiocarcinoma through the MNX1/Hippo axis

“…An important member of the Myc gene family, c-Myc, has been reported that its increased expression was associated with the progression of diverse cancers, including colorectal cancer, prostate cancer, lung cancer, HCC, bladder cancer, and cholangiocarcinoma [46][47][48][49][50][51][52][53][54] . In hepatobiliary cancers, c-Myc mediated small nuclear ribonucleoprotein polypeptides B (SNRPB) upregulation to facilitate the progression of HCC 54 .…”