Regulating pri/pre-microRNA up/down expressed in cancer proliferation, angiogenesis and metastasis using selected potent triterpenoids

MicroRNAs (miRNAs) play a crucial role in cancer progression by selectively inducing translational degradation of messenger RNA (mRNA) via sequence-specific interactions with the 3′-untranslated region (3'-UTR). The potential targeting of miRNA has been recognized as a significant avenue for investigating the biological progression of diverse cancer types. Consequently, targeting of pri-miRNA and pre-miRNA by phytochemicals emerges as a viable strategy in the realm of anticancer therapies. Among phytochemicals, triterpenoids have garnered significant recognition for their chemotherapeutic and chemopreventive capabilities in combating multiple cancers. To date, there is a dearth of literature about the molecular interactions between triterpenoids and miRNAs. The primary objective of this investigation is to discern the potential triterpenoids that can function as modulators for specific miRNAs, namely pri-miRNA-19b-2, pre-miR21, microRNA 20b, pri-miRNA-208a, pri-miRNA-378a, pri-miRNA-320b-2, and pri-miRNA-300, achieved through the use of in silico investigations. The study primarily focused on performing drug-likeness, computer-aided toxicity, and pharmacokinetic prediction studies for triterpenoids. Furthermore, molecular docking and simulation techniques were employed to investigate these compounds. The triterpenoids studied were shown to have drug-likeness characteristics, although asiatic acid, lupeol, and pristimerin were able to pass all toxicity tests. Among the triterpenoids that underwent docking, pristimerin had a significant binding energy of −10.9 kcal/mol during its interaction with pri-miR-378a. The stable interaction between the pristimerin and miRNA complex was demonstrated by molecular dynamics simulation. As a result, pristimerin has the potential to act as a modulator of carcinogenic miRNAs, making it a promising candidate for cancer prevention and treatment due to its tailored modulation of miRNA activity.