| Expression pattern: |
DN |
| Associated gene: |
SMARCA5 genomic DNA, SMARCA5, Pol II |
| Associated microRNA: |
- |
| Biological function: |
Inhibits DNA damage repair and increases sensitivity to cytotoxic drugs (cisplatin, bleomycin) in breast cancer cells. |
| Molecular mechanism: |
circSMARCA5 binds its parent gene locus and forms an R-loop at SMARCA5 exons 15-16, causing transcriptional pausing/termination at exon 15, downregulating SMARCA5 and producing truncated nonfunctional deltaSMARCA5, thereby impairing DNA repair and enhancing chemosensitivity. |
| Biological pathway or process: |
drug resistance (inhibits); other pathway/process (inhibits) |
| Detected method: |
Q
B
H
S
|
| Validation methods: |
RNA-seq; RT-qPCR; Northern Blot; ISH (In Situ Hybridization); Back-Splice Junction PCR / divergent primers PCR; RNase R Treatment; Sanger Sequencing; FISH / smFISH; Nuclear-Cytoplasmic Fractionation; Clinical Sample Validation; Luciferase Reporter Assay; ChIP / ChIP-seq; Transfection; Western Blot; CCK8; Colony Formation Assay; Cell Cycle Assay; Flow Cytometry（Non-apoptosis/cycle）; In Vivo Animal Model; IHC (Immunohistochemistry); IF (Immunofluorescence) |
| Clinical significance: |
circSMARCA5 may serve as a therapeutic target for drug-resistant breast cancer patients; blood circ-to-linear ratio of circSMARCA5 is lower in breast cancer patients than health volunteers, suggesting liquid biopsy potential. |
| Description: |
In breast cancer, circSMARCA5 is down-regulated in tumors and cell lines. circSMARCA5 binds the SMARCA5 genomic locus to form an R-loop, causing transcriptional termination around exon 15, reducing SMARCA5 and generating nonfunctional truncated deltaSMARCA5, thereby inhibiting DNA damage repair and increasing cisplatin/bleomycin sensitivity in vitro and in MCF-7 xenografts. |
| Confidence score: |
0.8576 |