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An integrative analysis reveals mechanisms of Prunella vulgaris in thyroid cancer metastasis
Shifan Zeng1, Benjuan Liu2, Rui Ge3
1Department of Pharmacy, Shanghai Changhai Hospital, the First Affiliated Hospital of Naval Medical University, Shanghai 200433, PR China; College of Basic Medical Sciences, Naval Medical University, Shanghai 200433, PR China.
Background:
Lymph node metastasis (LNM) in papillary thyroid carcinoma (PTC) is a major contributor to poor prognosis. Prunella vulgaris (P. vulgaris), a traditional medicinal herb, has shown potential in inhibiting PTC metastasis, but its molecular mechanism remains unclear.
Objectives:
This study aimed to elucidate the molecular mechanisms by which P. vulgaris exerts its anti-metastatic effects on PTC, focusing on identifying key active compounds and their target genes.
Methods:
RNA sequencing was used to identify differentially expressed genes (DEGs) between PTC and LNM tissues. Active compounds and targets of P. vulgaris were obtained from TCMSP and BATMAN-TCM and integrated with DEGs to construct a compound-target network. Machine-learning algorithms were applied to identify hub genes related to β-sitosterol (BS). The effects of BS and ADRB2 on cell viability, proliferation, migration, invasion, mitochondrial membrane potential (MMP), and reactive oxygen species (ROS) were examined in vitro.
Results:
696 DEGs and 195 P vulgaris targets were identified, with 91 overlapping genes intersecting DEGs and P. vulgaris targets. Within this network, 17 target genes were associated with BS, and five machine-learning algorithms consistently identified ADRB2 as a central hub. ADRB2 expression was significantly elevated in LNM tissues and closely correlated with clinicopathological features. BS treatment inhibited PTC cell growth and metastasis-related behaviors, which were reversed by ADRB2 overexpression.
Conclusion:
BS, an active component of P. vulgaris, inhibits key processes associated with PTC metastasis by targeting ADRB2 and inducing mitochondrial dysfunction. These findings not only provide the first experimental evidence linking BS to ADRB2-mediated anti-metastatic activity in PTC, but also offer a novel integrated approach for identifying therapeutic compounds from traditional herbs.
