The molecular mechanisms and targeting strategies of transcription factors in cholangiocarcinoma

ABSTRACT

Introduction

Cholangiocarcinoma consists of a cluster of malignant biliary tumors that tend to have a poor prognosis, ranking as the second most prevalent type of liver cancer, and their incidence rate has increased globally recently. The high-frequency driving mutations of cholangiocarcinoma, such as KRAS/IDH1/ARID1A/P53, imply the epigenetic instability of cholangiocarcinoma, leading to the dysregulation of various related transcription factors, thus affecting the occurrence and development of cholangiocarcinoma. Increasingly evidence indicates that the high heterogeneity and malignancy of cholangiocarcinoma are closely related to the dysregulation of transcription factors which promote cell proliferation, invasion, migration, angiogenesis, and drug resistance through reprogrammed transcriptional networks. It is of great significance to further explore and summarize the role of transcription factors in cholangiocarcinoma.

Areas covered

This review summarizes the oncogenic or tumor suppressive roles of key transcription factors in regulating cholangiocarcinoma progression and the potential targeting strategies of transcription factors in cholangiocarcinoma.

Expert opinion

Cholangiocarcinoma is a type of cancer highly influenced by transcriptional regulation, specifically transcription factors and epigenetic regulatory factors. Targeting transcription factors could be a potential and important strategy that is likely to impact future cholangiocarcinoma treatment.

KEYWORDS:

• Cholangiocarcinoma
• transcription factor
• epigenetics
• gene mutation
• molecular mechanisms
• drug target

Article highlights

• The high-frequency driving mutations of cholangiocarcinoma (CCA) suggest the epigenetic instability of CCA, leading to the dysregulation of various related transcription factors (TFs).

• TFs are not only affected by gene mutations but also closely related to epigenetic modulation in CCA.

• Oncogenic TFs in CCA have often activated abnormally and further drive pivotal events of CCA by affecting the transcription of downstream target genes or the activity of related signaling pathways.

• Tumor suppressor TF in CCA is often mutated or have a low expression.

This box summarizes key points contained in the article.

List of Abbreviations

Table

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China (81830107) awarded to QJ He, the National Natural Science Foundation of China (82104193), awarded to FJ Yan, and the Natural Science Foundation of Zhejiang Province (Grant no. LR19H310002) and the Westlake Laboratory (Westlake Laboratory of Life Sciences and Biomedicine) to H Zhu.