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Cross-border Regulation of the STK39/MAPK14 Pathway by Lycium Barbarum MiR166a to Inhibit Triple-negative Breast Cancer

Overview
Journal Am J Transl Res
Specialty General Medicine
Date 2024 Jul 15
PMID 39006277
Authors
Yujin Hou
Jing Li
Xuan Li
Ye Lv
Chunxiu Yuan
Jia Tian
Xinlan Liu
Affiliations
Soon will be listed here.
Abstract

Objective: To investigate the effects of Lycium barbarum miRNA166a (Lb-miR166a) on human gene expression regulation during the therapy for triple-negative breast cancer (TNBC).

Methods: 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.

Results: 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.

Conclusion: 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.

References
1.
de Paula B, Kieran R, Koh S, Crocamo S, Abdelhay E, Munoz-Espin D . Targeting Senescence as a Therapeutic Opportunity for Triple-Negative Breast Cancer. Mol Cancer Ther. 2023; 22(5):583-598. PMC: 10157365. DOI: 10.1158/1535-7163.MCT-22-0643. View
2.
Davalos A, Pinilla L, Lopez de Las Hazas M, Pinto-Hernandez P, Barbe F, Iglesias-Gutierrez E . Dietary microRNAs and cancer: A new therapeutic approach?. Semin Cancer Biol. 2020; 73:19-29. DOI: 10.1016/j.semcancer.2020.10.006. View
3.
Chiu M, Liu H, Wu Y, Shen M, Chou C . SPAK mediates KCC3-enhanced cervical cancer tumorigenesis. FEBS J. 2014; 281(10):2353-65. DOI: 10.1111/febs.12787. View
4.
Ni F, Hao S, Yang W . Multiple signaling pathways in Sertoli cells: recent findings in spermatogenesis. Cell Death Dis. 2019; 10(8):541. PMC: 6637205. DOI: 10.1038/s41419-019-1782-z. View
5.
Johnston A, Naselli G, Gonez L, Martin R, Harrison L, Deaizpurua H . SPAK, a STE20/SPS1-related kinase that activates the p38 pathway. Oncogene. 2000; 19(37):4290-7. DOI: 10.1038/sj.onc.1203784. View