Hepatocellular carcinoma (HCC) is the most common form of liver cancers , which has an annual incidence of at least 6 per 100,000 individuals and represents the fastest-rising cause of cancer-related death . Due to the high rate of recurrence and metastasis, the five-year survival rate for advanced HCC is poor. However, existing targeted drugs show unsatisfactory efficacy, due to a combination of factors spanning an array of different clinical and biological behaviors, and the development of anti-HCC drug resistance . The molecular mechanisms underlying tumor formation and progression are poorly understood, which further complicates the effective treatment of HCC . In addition, the lack of markers that are specific for tumor type or disease stage represents a critical gap in the current understanding and treatment of HCC.
Pre-mRNA splicing is a fundamental process that plays a considerable role in generating protein diversity. Pre-mRNA splicing is also the key to the pathology of numerous diseases, especially cancers . The connection between cancer biology and splicing regulation is of primary importance to understand the mechanisms leading to disease and also to improve the development of therapeutic approaches . Among the array of splicing factors, pre-mRNA processing factor 3 (PRPF3), a component of the U4/U6 di-snRNP, is required for U4/U6•U5 tri-snRNP formation and recruitment to active spliceosomes, which is essential for efficient pre-mRNA splicing [7, 8].
It is also known that one gene pair, KCNE2-PRPF3 as the signature could robustly predict prognoses of gastric cancer patients treated with 5-FU-based chemotherapy . As a member of the hepatic transcription factor network, Hepatocyte Nuclear Factor 4 Alpha (HNF4α) plays a pivotal role in liver development and hepatocellular differentiation. One study indicated that PRPF3 is an HNF4α regulated gene with induced expression in mouse and human HCC . However, the biological function of PRPF3 in HCC remains to be determined.
Here, we investigated PRPF3 expression and mutations in data from patients with HCC in The Cancer Genome Atlas (TCGA) and various public databases. Using multi-dimensional analysis, we evaluated genomic alterations and functional networks related to PRPF3 in HCC and explored its role in tumor immunity. Our results could potentially reveal new targets and strategies for HCC diagnosis and treatment.
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