| Expression pattern: |
DN |
| Associated gene: |
PTEN, Foxo3a, PI3K/AKT, P-gp/ABCB1, BCRP/ABCG2 |
| Associated microRNA: |
miR-556-5p, miR-1322 |
| Biological function: |
Suppresses CRC cell viability/proliferation and metastasis; promotes apoptosis; increases sensitivity to MEK inhibitors (overcomes MEK inhibitor resistance) in PIK3CA-mutant CRC. |
| Molecular mechanism: |
Activated PI3K/AKT phosphorylates Foxo3a to suppress circLHFPL2 transcription; circLHFPL2 functions as a ceRNA sponging miR-556-5p and miR-1322 to upregulate PTEN, forming a feedback loop affecting PI3K/AKT and drug-resistance proteins (P-gp/BCRP). |
| Biological pathway or process: |
PI3K/AKT (inhibits); proliferation (inhibits); apoptosis (promotes); metastasis (inhibits); ceRNA regulation (other); drug resistance (inhibits) |
| Detected method: |
Q
S
|
| Validation methods: |
RNA-seq; RT-qPCR; Back-Splice Junction PCR / divergent primers PCR; Sanger Sequencing; RNase R Treatment; FISH / smFISH; Nuclear-Cytoplasmic Fractionation; Clinical Sample Validation; Luciferase Reporter Assay; RIP (RNA Immunoprecipitation); RNA Pull-Down; Transfection; CCK8; Colony Formation Assay; Annexin V/PI Flow Cytometry; Western Blot; IHC (Immunohistochemistry); ChIP / ChIP-seq; In Vivo Animal Model; Survival Analysis; Bioinformatics Analysis |
| Clinical significance: |
Low circLHFPL2 expression is associated with poor overall survival in PIK3CA-mutant CRC patients. |
| Description: |
circLHFPL2 is downregulated in PIK3CA-mutant colorectal cancer and mainly localizes to the cytoplasm. It suppresses tumor progression by sponging miR-556-5p/miR-1322 to increase PTEN, thereby inhibiting PI3K/AKT signaling, and it can reverse PIK3CA-mediated MEK inhibitor resistance (via reducing P-gp/BCRP). |
| Confidence score: |
0.8931 |