Study on the mechanism of 18β-glycyrrhetinic acid inhibiting the proliferation of renal cancer cells by inducing autophagy through the miR-27a-5p/LC3 axis.

BACKGROUND: Renal carcinoma is a common, aggressive urinary tract malignancy with notable clinical challenges such as severe treatment toxicity and poor patient outcomes; 18β-glycyrrhetinic acid (18β-GA), an active component of Chinese herb Glycyrrhiza uralensis, has potent anti-tumor activity, while its role and molecular mechanisms in renal cancer remain elusive. AIM: This research investigates the mechanism through which 18β-GA suppresses renal cancer cell proliferation. METHODS: Combining whole transcriptome sequencing and network pharmacology, we identified 18β-GA-regulated key molecule miR-27a-5p and its core renal cancer targets; Cell assays confirmed 18β-GA-mediated suppression of renal cancer cell proliferation. Lentivirus-mediated miR-27a-5p modulation verified its role in renal cancer proliferation, and Western blot detection of autophagy marker LC3 expression clarified the miR-27a-5p/LC3 axis involvement in the anti-renal cancer effects of 18β-GA. RESULTS: Research shows 18β-GA may exert anti-renal cancer effects by targeting HMOX1, HCK, CASP1 and IDO1, with its mechanism linked to the autophagy pathway via functional enrichment analysis; whole transcriptome sequencing identified miR-27a-5p as the most significantly altered by 18β-GA in renal cancer cells. Experimental verification confirmed that 18β-GA downregulates miR-27a-5p to elevate the autophagy marker LC3II/LC3I ratio, activate autophagy, reduce 786-O and ACHN cell viability, promote apoptosis, inhibit colony formation, and thus suppress renal cancer cell proliferation. CONCLUSION: 18β-GA induces autophagy and inhibits proliferation of renal cancer cells by down-regulating miR-27a-5p and relieving its inhibition on the LC3-mediated autophagy pathway, suggesting that the miR-27a-5p/LC3 axis may be a key target for 18β-GA in the treatment of renal cancer.