Hou Yujin, Li Jing, Li Xuan, Lv Ye, Yuan Chunxiu, Tian Jia, Liu Xinlan
Department of Oncology, General Hospital of Ningxia Medical University Yinchuan, Ningxia, China.
Department of Special Technical Diagnosis and Treatment, Ning'an Hospital Yinchuan, Ningxia, China.
Am J Transl Res. 2024 Jun 15;16(6):2683-2698. doi: 10.62347/AQEW8179. eCollection 2024.
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.
探讨枸杞微小RNA166a（Lb-miR166a）在三阴性乳腺癌（TNBC）治疗过程中对人类基因表达调控的影响。
采用转录组测序分析枸杞果实中微小RNA的分布和组成。通过慢病毒转染将Lb-miR166a导入TNBC的MB-231细胞，以研究其在体内外对细胞增殖、凋亡、侵袭和转移的影响。通过生物信息学和双荧光素酶测定鉴定Lb-miR166a的靶基因。通过临床数据分析结合细胞研究阐明丝氨酸/苏氨酸蛋白激酶39（STK39）在TNBC进展中的作用。使用靶向特异性敲除的MB-231细胞系确认Lb-miR166a对STK39/丝裂原活化蛋白激酶14（MAPK14）通路的影响。
发现Lb-miR166a在枸杞中高表达。它抑制MB-231细胞的增殖、侵袭和转移，并促进细胞凋亡。STK39在TNBC中过表达，且与侵袭性增加和患者预后较差相关。基因富集分析和双荧光素酶测定表明，Lb-miR166a跨界调节STK39表达并抑制MAPK14磷酸化，影响下游靶基因的磷酸化。
Lb-miR166a下调STK39并随后抑制MAPK14磷酸化，导致TNBC细胞的增殖、迁移和侵袭减少。这些发现为TNBC治疗提出了一种新的治疗策略，突出了Lb-miR166a在管理这种侵袭性癌症类型中的潜在临床应用。
