Cross-regulation between microRNAs and key proteins of signaling pathways in hepatocellular carcinoma

ABSTRACT

Introduction

Hepatocellular carcinoma (HCC) is a subtype of primary liver cancer and a major cause of death. Although miRNA plays an important role in hepatocellular carcinoma, the specific regulatory network remains unclear. Therefore, this paper comprehensively describes the miRNA-related signaling pathways in HCC and the possible interactions among different signaling pathways. The aim is to lay the foundation for the discovery of new molecular targets and multi-target therapy.

Areas covered

Based on miRNA, HCC, and signaling pathways, the literature was searched on Web of Science and PubMed. Then, common targets between different signaling pathways were found from KEGG database, and possible cross-regulation mechanisms were further studied. In this review, we elaborated from two aspects, respectively, laying a foundation for studying the regulatory mechanism and potential targets of miRNA in HCC.

Expert opinion

Non-coding RNAs have become notable molecules in cancer research in recent years, and many types of targeted drugs have emerged. From the outset, molecular targets and signal pathways are interlinked, which suggests that signal pathways and regulatory networks should be concerned in basic research, which also provides a strong direction for future mechanism research.

KEYWORDS:

• MicroRNAs
• hepatocellular carcinoma
• signaling pathway
• interaction
• target

Article highlights

• HCC is the main cause of death in liver cancer. Currently, the combination of chemotherapy and targeted therapy has been well applied.

• Finding suitable targets is the key in targeted therapy, and non-coding RNAs such as miRNA have been widely studied as new molecular targets.

• This review summarizes the specific molecular mechanisms of miRNAs and common signaling pathways in hepatocellular carcinoma and mediates signaling pathway activation by regulating key proteins and kinases.

• The division in this paper focuses on different signaling pathways rather than phenotypes that have been reported in the literature.

• The interaction between different signal pathways is summarized.

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

The present study was supported from National Natural Science Foundation of China (grant number 82003802), the Natural Science Foundation of Hunan Province (grant number 2019JJ50542), the Science and Technology program of Hunan Health Commission (grant number 20201978), the China Scholarship Council (grant no. 201808430085), the Scientific Research Project of Hunan Provincial Education Department(grant number 21B0438), the Hengyang City Science and Technology Planning Project (grant number 202150063473), the Scientific Research Project of Hunan Provincial Health Commission (grant number 202202044140), the Undergraduate Research based Learning and Innovative Experimental Program of Hunan Province (grant number S202112650003 and S202112650005).