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PHF8 small interfering RNA
- Development stage
- Preclinical
- Modality
- Chemically Modified siRNA → Small Interfering RNA (siRNA) → Small RNA Therapeutics → RNA Therapeutics → Nucleic Acid Therapeutics, Conjugated siRNA → Small Interfering RNA (siRNA) → Small RNA Therapeutics → RNA Therapeutics → Nucleic Acid Therapeutics
- Administration
- Transfection (in Vitro/in Vivo Cell Culture; Investigational)
01
Overview
PHF8 small interfering RNA (siPHF8) is a research-grade RNA interference (RNAi) agent designed to silence the expression of the histone demethylase PHF8 (Plant Homeodomain Finger Protein 8). In the context of hepatocellular carcinoma (HCC), PHF8 has been identified as a critical epigenetic mediator of resistance to multikinase inhibitors (MKIs) such as sorafenib and lenvatinib. Mechanistically, the long non-coding RNA LMCD1-AS1 binds directly to PHF8, promoting H4K20me1 to epigenetically activate oncogenes like c-Myc and β-catenin, and upregulate lactate dehydrogenase A (LDHA). This interaction establishes a protumorigenic metabolic state characterized by lactate overproduction. Silencing PHF8 using siRNA has been shown to reverse LMCD1-AS1-driven resistance and restore drug sensitivity in HCC models, highlighting the LMCD1-AS1/PHF8/H4K20me1 axis as a potential therapeutic target.
- Other names
- small interfering RNA targeting PHF8PHF8-targeting siRNAPHF-8-targeting siRNAPHF 8-targeting siRNA
02
Targets
PHF8 (Histone lysine demethylase PHF8)
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