Cross-border regulation of the STK39/MAPK14 pathway by Lycium barbarum miR166a to inhibit triple-negative breast cancer.

Abstract

To investigate the effects of Lycium barbarum miRNA166a (Lb-miR166a) on human gene expression regulation during the therapy for triple-negative breast cancer (TNBC). Transcriptome sequencing was used to analyze the distribution and composition of miRNA in Lycium barbarum fruit. Lb-miR166a was introduced into TNBC MB-231 cells by lentiviral transfection to study its effects on cell proliferation, apoptosis, invasion, and metastasis both in vivo and in vitro. Bioinformatic and dual-luciferase assays identified the target gene of Lb-miR166a. The role of STK39 in TNBC progression was elucidated through clinical data analysis combined with cellular studies. The influence of Lb-miR166a on the STK39/MAPK14 pathway was confirmed using a target-specific knockout MB-231 cell line. Lb-miR166a was found to be highly expressed in Lycium barbarum. It inhibited MB-231 cell proliferation, invasion, and metastasis, and promoted apoptosis. STK39 was overexpressed in TNBC and was associated with increased invasiveness and poorer patient prognosis. Gene enrichment analysis and dual-luciferase assays demonstrated that Lb-miR166a regulates STK39 expression cross-border and inhibits MAPK14 phosphorylation, impacting the phosphorylation of downstream target genes. The downregulation of STK39 and subsequent inhibition of MAPK14 phosphorylation by Lb-miR166a leads to reduced proliferation, migration, and invasion of TNBC cells. These findings suggest a novel therapeutic strategy for TNBC treatment, highlighting possible clinical applications of Lb-miR166a in managing this aggressive cancer type.