Artemisinin inhibits colorectal cancer progression via the FAM83A-AS1/HIF-1α axis

Emerging evidence indicates that the lncRNA FAM83A-AS1 interacts closely with HIF-1α to modulate malignant biological behaviors and glycolytic metabolism in CRC. The mechanism underlying the effects of artemisinin on colorectal cancer (CRC) was investigated using a network pharmacology approach.

The action network of artemisinin was analyzed using network pharmacology. Stable FAM83A-AS1 and HIF-1α knockout cell models were established using a lentiviral system. The effects of artemisinin on cellular functions, including proliferation, metastasis, cell cycle progression, and glycolysis in CRC cells, were assessed through in vitro assays. The expression of HIF-1α was assessed by immunohistochemistry in tumor tissues from 219 patients with CRC, and its clinical associations were analyzed.

Artemisinin was predicted to target 96 proteins associated with CRC, including HIF-1α. Artemisinin inhibited proliferation, migration, and glycolysis, and induced cell cycle arrest in CRC cells. Artemisinin reduced the expression levels of Cyclin D1, CDK4, HIF-1α, PKM2, and N-cadherin. Artemisinin promoted proteasome-mediated degradation of HIF-1α protein. HIF-1α upregulated the expression of FAM83A-AS1, whereas knockdown of FAM83A-AS1 reduced HIF-1α expression levels. The expression level of HIF-1α in tumor tissues was significantly higher than that in adjacent non-tumor tissues. HIF-1α expression was associated with tumor node metastasis (TNM) stage, tumor (T)​stage, node (N)​stage, carcinoembryonic antigen (CEA) levels, recurrence, metastasis, and prognosis in patients with CRC.

Artemisinin promoted proteasome-mediated degradation of HIF-1α protein and inhibited CRC progression, potentially through the FAM83A-AS1/HIF-1α regulatory axis.