circRNA basic information
circBase ID: -
Name: hsa_circ_PAK1
Synonym: circPAK1
Host Gene: PAK1
Genomic location(hg19): -
Genomic location(hg38): -
Subcellular localization: cytoplasm; exosome
 
 
 
 
 
 
 
Disease basic information
MONDO ID:
0007256
MONDO name: hepatocellular carcinoma
Disease details: hepatocellular carcinoma / HCC
Disease DO ID:
684, 686
Disease MeSH ID:
D006528
Disease NCIt ID:
C3099
Disease ICD11 ID:
1294035808
Disease OMIM ID:
114550
Species: Human
Species details: Homo sapiens
Tissue specimen:

HCC tissues; adjacent non-tumor tissues / normal liver tissues

Cell lines:

Hep-G2; Focus; Hep-3B; MHCC-97 L; HCC-LM3 (LM3); YY8103; Huh-7; L02; HUVEC; LM3-LR; Hep-3B-LR; LM3-P; Hep-3B-P

In vivo animal model:

cell line-derived xenograft

circRNA-disease information
Expression pattern:
UP
Associated gene: 14-3-3zeta, YAP, p-LATS1/2, CTGF, CYR61, TEAD1-4
Associated microRNA: -
Biological function: promotes HCC cell proliferation, migration, invasion, metastasis and angiogenesis; inhibits apoptosis; promotes tumor growth and lung metastasis in vivo; induces lenvatinib resistance and can transmit resistance via exosomes
Molecular mechanism: binds 14-3-3zeta competitively with YAP, weakening 14-3-3zeta-mediated recruitment/cytoplasmic fixation of YAP and reducing YAP phosphorylation by p-LATS, thereby promoting YAP nuclear localization and inactivating the Hippo signaling pathway; exosomal transfer of circPAK1 confers lenvatinib resistance
Biological pathway or process:

Hippo/YAP (inhibits); proliferation (promotes); migration (promotes); invasion (promotes); metastasis (promotes); angiogenesis (promotes); apoptosis (inhibits); drug resistance (promotes)

Detected method:
Q
S
Validation methods:

circRNA-seq; RT-qPCR; Back-Splice Junction PCR / divergent primers PCR; RNase R Treatment; Sanger Sequencing; Actinomycin D / DRB Stability Assay; FISH / smFISH; Nuclear-Cytoplasmic Fractionation; Clinical Sample Validation; RNA-seq; RNA Pull-Down; RIP (RNA Immunoprecipitation); Co-IP; Western Blot; IF (Immunofluorescence); Transfection; CCK8; EdU Staining; Colony Formation Assay; Transwell Assay; Wound Healing Assay; Annexin V/PI Flow Cytometry; Tube Formation Assay; In Vivo Animal Model; H&E Staining; IHC (Immunohistochemistry); Bioinformatics Analysis; Survival Analysis

Clinical significance:

high expression of circPAK1 negatively correlated with OS and DFS and was associated with aggressive clinicopathological features

Description:

circPAK1 is upregulated in HCC tissues/cell lines and promotes proliferation, migration/invasion, metastasis and angiogenesis while inhibiting apoptosis. It binds 14-3-3zeta competitively with YAP, promoting YAP nuclear localization and Hippo pathway inactivation. circPAK1 is enriched in exosomes from lenvatinib-resistant cells and can transfer resistance to recipient HCC cells.

Confidence score:

0.8949

Other information
Title:

CircPAK1 promotes the progression of hepatocellular carcinoma via modulation of YAP nucleus localization by interacting with 14-3-3zeta.

Journal: Journal of experimental & clinical cancer research : CR
Published: 2022
PubMed ID: 36131287
Study type:

combined biological and clinical study

Data availability: All data generated or analyzed during this study are included in this published article [and its supplementary information files].
Code availability: -