ORIGINAL RESEARCH article
Front. Oncol.
Sec. Genitourinary Oncology
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
Provisionally accepted- Ningxia Medical University, Yinchuan, China
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Abstract 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.
Keywords: 18β-glycyrrhetinic acid, Autophagy, miR-27a-5p/LC3 axis, proliferation, renal carcinoma
Received: 08 Dec 2025; Accepted: 13 Feb 2026.
Copyright: © 2026 Jia, Zhang, Li, Xu, Yang, Zhou, Liu, Zhao, Yuan and Nan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Ling Yuan
Yi Nan
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