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FOXC2 antisense RNA 1 (FOXC2-AS1)
- Target
- FOXC2-AS1
- Molecular classification
- Long noncoding RNA (lncRNA), Antisense RNA transcript, Noncoding gene product
01
Overview
FOXC2 antisense RNA 1 (FOXC2-AS1) is a long noncoding RNA transcribed antisense to the FOXC2 gene, with exon 1 fully complementary to FOXC2 mRNA. FOXC2-AS1 forms an RNA duplex with FOXC2 mRNA, enhancing its stability and protein expression. This mechanism drives proliferation, invasion, metastasis, and drug resistance in various cancers, especially colorectal cancer and osteosarcoma. Elevated FOXC2-AS1 is associated with poor prognosis, lymphovascular invasion, distant metastasis, and is implicated as a therapeutic target for suppressing tumor progression and overcoming chemoresistance. FOXC2-AS1 also plays key regulatory roles in liver fibrosis via modulation of hepatic stellate cell activation.
- Other names
- FOXC2 antisense RNA 1FOXC2-AS1ODRUL (osteosarcoma doxorubicin-resistance related upregulated lncRNA)
02
Mechanism of action
Antisense or RNA interference strategies to silence FOXC2-AS1 can reduce FOXC2 mRNA stability and protein expression, suppressing cancer growth and overcoming drug resistance. Targeting FOXC2-AS1 can downregulate FOXC2/ABCB1 axis, sensitizing tumor cells to doxorubicin.
03
Biological functions
Regulation of sense gene (FOXC2) mRNA stability via RNA duplex formationPost-transcriptional regulation of gene expressionPromotes cell proliferation, migration, and invasion in multiple cancersEnhances chemoresistance (notably to doxorubicin) in osteosarcomaModulates cellular signaling relevant for metastasis (intracellular Ca2+ dynamics and FAK signaling)Influences matrix stiffness-induced hepatic stellate cell activation and liver fibrosis
04
Disease associations
Cancer (colorectal, breast, prostate, non-small-cell lung cancer, osteosarcoma, liver fibrosis)Drug resistance (notably doxorubicin resistance in osteosarcoma)Fibrosis (liver fibrosis)
05
Safety considerations
Therapeutic targeting of lncRNAs presents challenges such as delivery specificity, potential off-target effects, and unknown long-term safety profilesFunctional redundancy or compensation by other lncRNAs may limit efficacy
06
Interacting drugs
Doxorubicin (resistance is regulated via FOXC2-AS1’s control of FOXC2 and downstream ABCB1)
07
Biomarkers
FOXC2-AS1 expression itself serves as a prognostic biomarker for poor survival and metastasis in colorectal cancer and osteosarcomaFOXC2-AS1/FOXC2 axis for predicting doxorubicin resistance
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