Han Xiao, Wei Linlin, Wu Bin
Oncology Ward 5, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning Province, People's Republic of China.
Medical Center, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning Province, People's Republic of China.
Onco Targets Ther. 2020 Apr 21;13:3347-3357. doi: 10.2147/OTT.S239730. eCollection 2020.
To explore the effects of protein arginine methyltransferase 5 (PRMT5) on the biological function of breast cancer cells (BCCs) by regulating the liver X receptor α (LXRα)/NF-κBp65 pathway.
A total of 80 patients with breast cancer (BC) admitted to our hospital were collected, and 80 breast cancer tissue specimens and 80 corresponding tumor-adjacent tissue specimens were sampled from them for analysis. The reverse transcription-polymerase chain reaction (RT-PCR) was employed to determine the expression of PRMT5 mRNA in the sampled tissues, and the Western blot to determine the expression of LXRα and NF-κBp65 proteins in the tissues and cells. The patients were followed up to analyze their 3-year survival rate. Stable and transient overexpression vectors and inhibition vectors were constructed and transfected into BCCs. The cell counting kit-8 (CCK8), transwell, and flow cytometry were adopted to analyze the proliferation, invasion, and apoptosis of transfected cells, on which the effects of PRMT5 on LXRα and NF-κBp65 proteins were analyzed.
PRMT5 was highly expressed in BC patients, and LXRα was lowly expressed in them, which had a high diagnostic value. Patients with high expression of PRMT5 showed a poor prognosis, and the expression of PRMT5 was related to the tumor size, pathological stage, differentiation, and metastatic in BC patients. Overexpressed PRMT5 enhanced the cell proliferation, invasion, and glycolysis abilities, weakened apoptosis ability, further lowered expression of LXRα and increased expression of NF-κBp65, while inhibited PRMT5 caused opposite results in those aspects. Up-regulating the expression of LXRα suppressed the proliferation, invasion, and aerobic glycolysis of BCCs and promoted their apoptosis, while inhibiting it posed opposite effects. The rescue experiment revealed that down-regulating the expression of PRMT5 could counteract the promotion of down-regulation of LXRα on proliferation, invasion and glycolysis of BCCs, and the nude mouse tumorigenesis test revealed that PRMT5 induced tumor on nude mice by mediating LXRα/NF-κBp65.
Inhibition of the PRMT5 expression can accelerate apoptosis of BCCs and weaken their proliferation, invasion, and aerobic glycolysis through the LXRα/NF-κBp65 pathway.
通过调节肝X受体α（LXRα）/核因子κB p65（NF-κBp65）通路，探讨蛋白质精氨酸甲基转移酶5（PRMT5）对乳腺癌细胞（BCCs）生物学功能的影响。
收集我院收治的80例乳腺癌患者，采集80份乳腺癌组织标本及80份相应的癌旁组织标本进行分析。采用逆转录-聚合酶链反应（RT-PCR）检测标本中PRMT5 mRNA的表达，采用蛋白质免疫印迹法检测组织及细胞中LXRα和NF-κBp65蛋白的表达。对患者进行随访，分析其3年生存率。构建稳定和瞬时过表达载体及抑制载体并转染至BCCs。采用细胞计数试剂盒-8（CCK8）、Transwell小室实验和流式细胞术分析转染细胞的增殖、侵袭及凋亡情况，并分析PRMT5对LXRα和NF-κBp65蛋白的影响。
PRMT5在乳腺癌患者中高表达，LXRα低表达，具有较高的诊断价值。PRMT5高表达患者预后较差，PRMT5表达与乳腺癌患者的肿瘤大小、病理分期、分化程度及转移情况相关。过表达PRMT5增强细胞增殖、侵袭及糖酵解能力，减弱凋亡能力，进一步降低LXRα表达并增加NF-κBp65表达，而抑制PRMT5则在这些方面产生相反结果。上调LXRα表达可抑制BCCs的增殖、侵袭及有氧糖酵解并促进其凋亡，而抑制LXRα表达则产生相反作用。挽救实验显示，下调PRMT5表达可抵消LXRα下调对BCCs增殖、侵袭及糖酵解的促进作用，裸鼠成瘤实验显示PRMT5通过介导LXRα/NF-κBp65诱导裸鼠成瘤。
抑制PRMT5表达可通过LXRα/NF-κBp65通路加速BCCs凋亡，减弱其增殖、侵袭及有氧糖酵解能力。
