PCBP1 regulates the transcription and alternative splicing of metastasis‑related genes and pathways in hepatocellular carcinoma

Abstract

PCBP1 is a multifunctional RNA-binding protein (RBP) expressed in most human cells and is involved in posttranscriptional gene regulation. PCBP1 regulates the alternative splicing, translation and RNA stability of many cancer-related genes and has been identified as a potential tumour suppressor gene. PCBP1 inhibits the invasion of hepatocellular carcinoma (HCC) cells, but there are few studies on the specific regulatory target and mechanism of RBPs in HCC, and it is unclear whether PCBP1 plays a role in tumour metastasis as a splicing factor. We analysed the regulation of gene expression by PCBP1 at the transcriptional level. We obtained and analysed PCBP1-knockdown RNA-seq data and eCLIP-seq data of PCBP1 in HepG2 cells and found that PCBP1 widely regulates the alternative splicing and expression of genes enriched in cancer-related pathways, including extracellular matrix, cell adhesion, small molecule metabolic process and apoptosis. We validated five regulated alternative splicing events affected by PCBP1 using RT-qPCR and found that there was a significant difference in the expression of APOC1 and SPHK1 between tumour and normal tissues. In this study, we provided convincing evidence that human PCBP1 profoundly regulates the splicing of genes associated with tumour metastasis. These findings provide new insight into potential markers or therapeutic targets for HCC treatment.

PolyC-RNA-binding protein 1 (PCBP1) enhances tropomyosin 3 (TPM3) mRNA stability to promote the progression of esophageal squamous cell carcinoma

“…Via eCLIP-sequence analysis to identify PCBP1-interacting transcripts in hepatocellular carcinoma cells, it was found that PCBP1 reads were preferentially enriched in 3′UTR and CDS regions. Notably, a total of 145 genes that were identified to bind to PCBP1 underwent alternative splicing under the regulation of PCBP1 at the same time [ 35 ]. Other works in various human cancer cells uncovered that PCBP1 binds to p27 mRNA 3’-UTR region via 5’-AUUAAGUAAU-3’ to repress tumor cell transformation and carcinogenesis [ 29 ].…”

A risk prediction model mediated by genes of APOD/APOC1/SQLE associates with prognosis in cervical cancer

“…According to previous studies, APOD was an immune-related gene and is associated with the risk of multiple types of cancer such as gastric cancer [ 28 ], thyroid cancer [ 29 ], breast cancer and cervical cancer [ 30 ], which was also considered as one of prognostic signatures in cancer. APOC1 was reported as an oncogene to promote tumorigenesis and progression of glioblastoma [ 31 ], gastric cancer [ 32 ], hepatocellular carcinoma [ 33 ], breast cancer [ 34 ] and so on. SQLE is a key enzyme of cholesterol biosynthesis [ 35 ] and tends to be over-expressed along with treatment sensitivity in colon cancer [ 36 ], breast cancer and non-small cell lung cancer [ 37 ], Acute Myeloid Leukemia [ 38 ] and pancreatic cancer [ 39 ].…”

Liver-specific lncRNA FAM99A may be a tumor suppressor and promising prognostic biomarker in hepatocellular carcinoma

“…These seven proteins play crucial roles in tumor occurrence and development. PCBP1 is a multifunctional RBP that regulates the alternative splicing, translation, and RNA stability of many cancer-related genes to exert its cancer-inhibiting effect [51][52][53]. SRSF5 and SRSF6 belong to the serine/arginine-rich (SR) protein family, which is an important class of splicing regulators.…”