Molecular targets and mechanisms of different aberrant alternative splicing in metastatic liver cancer

Abstract

Metastasis remains a major challenge in the successful management of malignant diseases. The liver is a major site of metastatic disease and a leading cause of death from gastrointestinal malignancies such as colon, stomach, and pancreatic cancers, as well as melanoma, breast cancer, and sarcoma. As an important factor that influences the development of metastatic liver cancer, alternative splicing drives the diversity of RNA transcripts and protein subtypes, which may provide potential to broaden the target space. In particular, the dysfunction of splicing factors and abnormal expression of splicing variants are associated with the occurrence, progression, aggressiveness, and drug resistance of cancers caused by the selective splicing of specific genes. This review is the first to provide a detailed summary of the normal splicing process and alterations that occur during metastatic liver cancer. It will cover the role of alternative splicing in the mechanisms of metastatic liver cancer by examining splicing factor changes, abnormal splicing, and the contribution of hypoxia to these changes during metastasis.

Keywords: Alternative splicing, Carcinoma, Hepatocellular, Metastasic, Liver neoplasms, Prognosis

Core Tip: Metastatic liver cancer refers to tumors formed outside the liver that metastasize to the liver and colonize it. Abnormal alternative splicing is a molecular characteristic unique to almost all tumor types. Most tumors exhibit a wide range of splicing abnormalities compared to the surrounding healthy tissues. This review is the first to provide a detailed summary of the normal splicing process and alterations that occur during metastatic liver cancer by examining splicing factor changes, abnormal splicing, and the contribution of hypoxia to cellular changes.