circRNA basic information
circBase ID: hsa_circ_0031607
Name: hsa_circ_SNX6
Synonym: circSNX6
Host Gene: SNX6
Genomic location(hg19): chr14:35044961-35078948:-
Genomic location(hg38): chr14:34575755-34609742:-
Subcellular localization: cytoplasm
 
 
 
 
 
 
 
Disease basic information
MONDO ID:
0005086
MONDO name: renal cell carcinoma
Disease details: renal cell carcinoma / RCC
Disease DO ID:
4450
Disease MeSH ID:
D002292
Disease NCIt ID:
-
Disease ICD11 ID:
-
Disease OMIM ID:
-
Species: Human
Species details: Homo sapiens
Tissue specimen:

tumor specimens; tumor and adjacent normal tissue specimens; RCC samples

Cell lines:

786-O; ACHN; HEK-293T; 7-R; A-R

In vivo animal model:

cell line-derived xenograft

circRNA-disease information
Expression pattern:
UP
Associated gene: GPCPD1, lysophosphatidic acid, LPA, SNX6
Associated microRNA: miR-1184
Biological function: circSNX6 promotes sunitinib resistance in RCC, increases IC50 and colony formation under sunitinib treatment, inhibits sunitinib-induced apoptosis, and serves as a prognostic biomarker for worse outcomes.
Molecular mechanism: circSNX6 functions as a cytoplasmic ceRNA/molecular sponge for miR-1184, relieving miR-1184-mediated suppression of GPCPD1, increasing intracellular LPA levels and promoting sunitinib resistance.
Biological pathway or process:

ceRNA regulation (promotes); drug resistance (promotes); apoptosis (inhibits); proliferation (promotes); lipid metabolism (promotes)

Detected method:
Q
S
Validation methods:

Back-Splice Junction PCR / divergent primers PCR; RNase R Treatment; Sanger Sequencing; circRNA-seq; Actinomycin D / DRB Stability Assay; RT-qPCR; Northern Blot; FISH / smFISH; Nuclear-Cytoplasmic Fractionation; Clinical Sample Validation; RIP (RNA Immunoprecipitation); RNA Pull-Down; Luciferase Reporter Assay; Transfection; CCK8; Colony Formation Assay; Annexin V/PI Flow Cytometry; In Vivo Animal Model; IHC (Immunohistochemistry); Western Blot; Cohort Study; Survival Analysis; Bioinformatics Analysis

Clinical significance:

High circSNX6 expression was correlated with sunitinib resistance, higher histologic grade, shorter PFS and OS, and could serve as an independent prognostic factor and biomarker for sunitinib response and survival in RCC patients.

Description:

circSNX6 is upregulated in sunitinib-resistant RCC cells and tumors and promotes sunitinib resistance in vitro and in vivo. Mechanistically, cytoplasmic circSNX6 sponges miR-1184 to upregulate GPCPD1 and increase intracellular LPA levels. High circSNX6 expression is associated with sunitinib resistance and poorer OS/PFS in RCC patients.

Confidence score:

0.8993

Other information
Title:

Circular RNA circSNX6 promotes sunitinib resistance in renal cell carcinoma through the miR-1184/GPCPD1/ lysophosphatidic acid axis.

Journal: Cancer letters
Published: 2021
PubMed ID: 34626691
Study type:

combined biological and clinical study

Data availability: TCGA; Supplementary data at https://doi.org/10.1016/j.canlet.2021.10.003
Code availability: -