Department of Anesthesiology, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Number 195, Tongbai Road, Zhengzhou, Henan Province, 450000, China.
Department of Hospital Infections, Shuguang Hospital Affiliated with Shanghai University of Traditional Chinese Medicine, Number 187, Puan Road, Shanghai, 200021, China.
BMC Cancer. 2018 Mar 9;18(1):255. doi: 10.1186/s12885-018-4031-4.
Breast cancer is one of the leading causes of death in women worldwide. Fast growth is the important character of breast cancer, which makes sure the subsequent metastasize and invasion breast cancer. Golgi related genes GOLPH3 has been reported to regulate many kinds of cancers proliferation. However, its upregulator remains largely unknown. miRNA modulate gene expression by post-transcriptional repression to participate in many signaling pathway of breast cancer cell proliferation. miR-590 has been reported to regulate tumorgenesis and could be regulated by its own target ATF-3. But whether miR-590 can be the modulator of Golgi related genes to regulate the breast cancer proliferation is unclear.
We performed the bioinformatics analysis of survival rate and expression differences of patients using the data of The Cancer Genome Atlas (TCGA).Both of MTS and BrdU assays were used for cell proliferation analysis. Cell cycle was detected by flow cytometry .qRT-PCR was used for detecting the cell cycle related gene expression. Student's t-test or One way anova was used for statistics.
We found the upregulation of GOLPH3 in breast cancer samples compared with normal breast tissues, which also was related to the poor prognosis. Overexpression of GOLPH3 significantly promoted proliferation both of MDA-MB-231 cells (ER negative) and MCF-7 cells (ER positive). We further found that miRNA-590-3p could directly target the 3'-UTR of GOLPH3 mRNA to repress its expression. Overexpression of miR-590-3p inhibited the proliferation of MDA-MB-231 and MCF-7 cells. The rescue experiments indicated that overexpression of GOLPH3 significantly resorted the proliferation inhibited by miR-590-3p. We also found that ATF-3 repressed miR-590-3p expression to modulate miR-590/GOLPH3 pathway to regulate breast cancer cells proliferation.
This study not only suggests that the ATF-3/miR-590/GOLPH3 signaling pathway is critically involved in the proliferation of breast cancer cells, but provides a novel therapeutic target and new insight base on epigenetic regulation for future breast cancer diagnosis and clinical treatment.
乳腺癌是全球女性死亡的主要原因之一。快速生长是乳腺癌的重要特征，这确保了随后的转移和侵袭乳腺癌。高尔基相关基因 GOLPH3 已被报道调节多种癌症的增殖。然而，其上调因子在很大程度上仍然未知。miRNA 通过转录后抑制来调节基因表达，从而参与乳腺癌细胞增殖的许多信号通路。miR-590 已被报道可调节肿瘤发生，并且可以受其自身靶标 ATF-3 的调节。但是，miR-590 是否可以作为高尔基相关基因的调节剂来调节乳腺癌增殖尚不清楚。
我们使用癌症基因组图谱（TCGA）的数据进行了患者生存率和表达差异的生物信息学分析。使用 MTS 和 BrdU 测定法进行细胞增殖分析。通过流式细胞术检测细胞周期。qRT-PCR 用于检测细胞周期相关基因的表达。使用 Student's t-test 或 One way anova 进行统计分析。
我们发现与正常乳腺组织相比，乳腺癌样本中 GOLPH3 的表达上调，这也与不良预后相关。GOLPH3 的过表达显着促进了 MDA-MB-231 细胞（ER 阴性）和 MCF-7 细胞（ER 阳性）的增殖。我们进一步发现，miRNA-590-3p 可以直接靶向 GOLPH3 mRNA 的 3'-UTR 以抑制其表达。miR-590-3p 的过表达抑制了 MDA-MB-231 和 MCF-7 细胞的增殖。挽救实验表明，GOLPH3 的过表达显着挽救了由 miR-590-3p 抑制的增殖。我们还发现 ATF-3 抑制 miR-590-3p 的表达以调节 miR-590/GOLPH3 通路来调节乳腺癌细胞的增殖。
本研究不仅表明 ATF-3/miR-590/GOLPH3 信号通路在乳腺癌细胞增殖中起关键作用，而且为未来乳腺癌的诊断和临床治疗提供了基于表观遗传调控的新的治疗靶标和新的见解。
