CPSF4 regulates circRNA formation and microRNA mediated gene silencing in hepatocellular carcinoma

Dong, Jiani; Li, Xiaojing; Zhang, Cheng; Zhu, Qubo

doi:10.1038/s41388-021-01867-6

Cited by 16 publications

(5 citation statements)

References 44 publications

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“…Previous research has shown that CPSF4 is overexpressed in a number of cancer types and is related to prognosis (Zhang et al 2021 ; Wu et al 2019 ; Yi et al 2016 ). However, previous studies on CPSF4 in liver cancer were limited to its polyadenylation mechanism (Wang et al 2021b ). It is necessary to further explore the regulatory role of CPSF4 on AS gene and its role in malignant phenotype, prognosis, and tumor microenvironment of liver cancer.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive analysis of CPSF4-related alternative splice genes in hepatocellular carcinoma

Yuemaierabola,

Guo,

Sun

et al. 2023

J Cancer Res Clin Oncol

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Background An important stage in controlling gene expression is RNA alternative splicing (AS), and aberrant AS can trigger the development and spread of malignancies, including hepatocellular carcinoma (HCC). A crucial component of AS is cleavage and polyadenylation-specific factor 4 (CPSF4), a component of the CPSF complex, but it is unclear how CPSF4-related AS molecules describe immune cell infiltration in the total tumor microenvironment (TME). Methods Using RNA-sequencing data and clinical data from TCGA-LIHC from the Cancer Genome Atlas (TCGA) database, the AS genes with differential expression were found. The univariate Cox analysis, KM analysis, and Spearman analysis were used to identify the AS genes related to prognosis. Screening of key AS genes that are highly correlated with CPSF4. Key genes were screened using Cox regression analysis and stepwise regression analysis, and prognosis prediction models and the topography of TME cell infiltration were thoroughly analyzed. Results A model consisting of seven AS genes (STMN1, CLSPN, MDK, RNFT2, PRR11, RNF157, GHR) was constructed that was aimed to predict prognostic condition. The outcomes of the HCC samples in the high-risk group were considerably worse than those in the lower risk group (p < 0.0001), and different risk patient groups were formed. According to the calibration curves and the area under the ROC curve (AUC) values for survival at 1, 2, and 3 years, the clinical nomogram performs well in predicting survival in HCC patients. These values were 0.76, 0.70, and 0.69, respectively. Moreover, prognostic signature was markedly related to immune infiltration and immune checkpoint genes expression. Conclusion By shedding light on the function of CPSF4 and the seven AS genes in the formation and progression of HCC, this research analysis contributes to the development of more useful prognostic, diagnostic, and possibly therapeutic biomarkers.

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Section: Discussionmentioning

confidence: 99%

Comprehensive analysis of CPSF4-related alternative splice genes in hepatocellular carcinoma

Yuemaierabola,

Guo,

Sun

et al. 2023

J Cancer Res Clin Oncol

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“…The high expression of CPSF4 in HCC also corresponds to the overall down-regulation of circular RNA. Further studies demonstrated that overexpression of CPSF4 could promote the proliferation of HCC cells and was closely related to the clinicopathological characteristics of HCC patients [49].…”

Section: Cleavage Factorsmentioning

confidence: 96%

“…The PAS element can be recognized by the cleavage factors to promote the cleavage of the circRNA and reduce its expression. Recent studies have shown that CPSF4 can inhibit the formation of circRNA by recognizing and cutting the AAUAAA motif on pre-mRNA, thereby inhibiting the proliferation of HCC cells, which is of great significance to the prognosis of HCC patients [49].…”

Section: Splice Sitesmentioning

confidence: 99%

Mechanisms Regulating Abnormal Circular RNA Biogenesis in Cancer

Huang

Zhu

2021

Cancers

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Circular RNAs (circRNAs), which are a class of endogenous RNA with covalently closed loops, play important roles in epigenetic regulation of gene expression at both the transcriptional and post-transcriptional level. Accumulating evidence demonstrated that numerous circRNAs were abnormally expressed in tumors and their dysregulation was involved in the tumorigenesis and metastasis of cancer. Although the functional mechanisms of many circRNAs have been revealed, how circRNAs are dysregulated in cancer remains elusive. CircRNAs are generated by a “back-splicing” process, which is regulated by different cis-regulatory elements and trans-acting proteins. Therefore, how these cis and trans elements change during tumorigenesis and how they regulate the biogenesis of circRNAs in cancer are two questions that interest us. In this review, we summarized the pathways for the biogenesis of circRNAs; and then illustrated how circRNAs dysregulated in cancer by discussing the changes of cis-regulatory elements and trans-acting proteins that related to circRNA splicing and maturation in cancer.

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“…Another study focused on the modulation of circRNA expression in HCC and showed that high expression of CPSF4 can reduce circRNA expression by recognizing the polyadenylation site and the inhibition of circRNA/miRNA pathway was associated with poor prognosis. 55 These studies on the regulatory mechanism of circRNA biogenesis may elucidate HCC tumorigenesis and make cancer-associated circRNAs promising candidates as potential therapeutic targets.…”

Section: Circrnas In Hccmentioning

confidence: 99%