基因芯片初步探讨乳腺癌转移相关蛋白Nucleobindin-2介导的信号通路

doi:10.3969/j.issn.1000-8535.2022.02.013

广州医药 ›› 2022, Vol. 53 ›› Issue (2): 56-67.DOI: 10.3969/j.issn.1000-8535.2022.02.013

基因芯片初步探讨乳腺癌转移相关蛋白Nucleobindin-2介导的信号通路

符青云¹, 欧阳小明², 郅程², 曾亮³

1 广东省江门市五邑中医院病理科(江门 529031)
2 广州医科大学附属第二医院病理科(广州 510260)
3 广州市妇女儿童医疗中心病理科(广州 510623)

收稿日期:2021-09-23 发布日期:2022-04-12
通讯作者: 曾亮,E-mail:zlxx03@126.com
基金资助:
湖南省卫生计生委科研计划课题(B2017097)

Study of breast cancer metastasis associated protein nucleobindin-2 mediated signal pathway by gene chip

FU Qingyun¹, OUYANG Xiaoming², ZHI Cheng², ZENG Liang³

1 Department of Pathology, Wuyi Traditional Chinese Medicine Hospital, Jiangmen 529031, China
2 Department of Pathology, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, China
3 Department of Pathology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, China

Received:2021-09-23 Published:2022-04-12

摘要/Abstract

摘要： 目的探讨核结合蛋白2(NUCB2)介导的下游信号分子和通路,为阐明NUCB2在乳腺癌中的功能提供依据。方法构建NUCB2-RNAi慢病毒载体,感染MDA-MB-231细胞株。然后将MDA-MB-231分为阴性对照病毒感染细胞组(NC组)、感染NUCB2基因shRNA病毒细胞组(KD组),用Affymetrix基因表达谱芯片对NUCB2下游基因进行筛选,并对所有数据进行独创性通路分析(IPA)分析。用qPCR测定mRNA水平。统计采用SPSS 20.0软件。结果 Path-Array研究筛选了KD组与NC组的差异基因,其中上调基因186个,下调基因356个,部分差异表达基因的检测表明,这些基因的mRNA水平与Path-Array筛选结果一致。IPA分析显示,经典途径中差异表达基因的显著富集表明胆固醇生物合成的超途径被显著抑制。上游调节因子分析显示了所有不同表达基因的上游调节因子,包括转录因子、细胞因子、小RNA、受体、激酶、化学分子和药物。疾病和功能差异表达基因的显著丰富表明,与NUCB2相关的差异表达基因与41种疾病和功能显著相关,更多与癌症、组织损伤和异常相关。结论 NUCB2的功能涉及多种基因和多种信号通路。

关键词: 乳腺癌, 通路, 基因芯片, 核结合蛋白2

Abstract: Objective In order to further explore the downstream signal molecules and pathways mediated by nucleobindin-2 (NUCB2), to provide a basis for elucidating the significance of NUCB2 in breast cancer. Method NUCB2-RNAi lentivirus vector was constructed and infecting MDA-MB-231 cell line.Then MDA-MB-231 cells were divived into two group, cells with negative control virus infection (NC group) and cells infected with NUCB2 gene shRNA virus (KD group). NUCB2 downstream gene screening was conducted by Affymetrix gene expression profiling Path-Array chip and all data were analyzed by ingenuity pathway analysis (IPA). The mRNA level was detected by qPCR. SPSS 20.0 software was used for statistics. Results Path-Array study screened out differential genes between KD and NC group which the number of up-regulated genes was 186, the number of down-regulated genes was 356.Detection of some differentially expressed genes showed that the mRNA levels of these genes were consistent with the results of Path-Array screening.IPA analysis revealed that significant enrichment of differentially expressed genes in the classical pathway showed superpathway of cholesterol biosynthesis was significantly inhibited.The upstream regulatory factor analysis showed the upstream regulatory factors of all the differentially expressed genes, including transcription factors, cytokine, small RNA, receptors, kinases, chemical molecules and drugs.The significant enrichment of differentially expressed genes in disease and function showed that NUCB2 associated differentially expressed genes were significantly related with 41 diseases and functions, which were more related with cancer, organismal injury and abnormities. Conclusion The function of NUCB2 involved multiple genes and multiple signaling pathways.

Key words: breast cancer, pathway, gene chip, nucleobindin-2

符青云, 欧阳小明, 郅程, 曾亮. 基因芯片初步探讨乳腺癌转移相关蛋白Nucleobindin-2介导的信号通路[J]. 广州医药, 2022, 53(2): 56-67.

FU Qingyun, OUYANG Xiaoming, ZHI Cheng, ZENG Liang. Study of breast cancer metastasis associated protein nucleobindin-2 mediated signal pathway by gene chip[J]. Guangzhou Medical Journal, 2022, 53(2): 56-67.

参考文献

[1] LIANG Z, ZHONG J G, HE G C, et al. Identification of nucleobindin-2 as a potential biomarker for breast cancer metastasis using iTRAQ-based quantitative proteomic analysis[J].J Cancer, 2017,8(15): 3062-3069.
[2] KAN J Y, YEN M C, WANG J Y, et al. Nesfatin-1/Nucleobindin-2 enhances cell migration, invasion, and epithelial-mesenchymal transition via LKB1/AMPK/TORC1/ZEB1 pathways in colon cancer[J].Oncotarget, 2016, 7(21):31336-31349.
[3] XU Y, PANG X, DONG M, et al. Nesfatin-1 inhibits ovarian epithelial carcinoma cell proliferation in vitro[J].Biochem Biophys Res Commun, 2013, 440(4): 467-472.
[4] ISHIDA E, HASHIMOTO K, SHIMIZU H, et al.Nesfatin-1 induces the phosphorylation levels of cAMP response element-binding protein for intracellular signaling in a neural cell line[J].PLoS One, 2012;7(12):e50918.
[5] VALENCIA C A, COTTEN S W, DUAN J, et al.Modulation of nucleobindin-1 and nucleobindin-2 by caspases[J].FEBS Lett, 2008, 582(2):286-290.
[6] OZCAN M, GOK Z B, KACAR E, et al. Nesfatin-1 increases intracellular calcium concentration by protein kinase C activation in cultured rat dorsal root ganglion neurons[J].Neurosci Lett, 2016(619):177-181.
[7] IWASAKI Y, NAKABAYASHI H, KAKEI M, et al.Nesfatin-1 evokes Ca²⁺ signaling in isolated vagal afferent neurons via Ca²⁺ influx through N-type channels[J].Biochem Biophys Res Commun, 2009, 390(3):958-962.
[8] de ALBA E, TJANDRA N.Structural studies on the Ca²⁺-binding domain of human nucleobindin (calnuc)[J].Biochemistry.2004, 43(31):10039-10049.
[9] TANG C H, FU X J, XU X L, et al. The anti-inflammatory and anti-apoptotic effects of nesfatin-1 in the traumatic rat brain[J].Peptides,2012, 36(1):39-45.
[10] RAMANJANEYA M, TAN B K, RUCINSKI M, et al. Nesfatin-1 inhibits proliferation and enhances apoptosis of human adrenocortical H295R cells[J].J Endocrinol.2015, 226(1):1-11.
[11] TAKAGI K, MIKI Y, TANAKA S,et al. Nucleobindin 2 (NUCB2) in human endometrial carcinoma: a potent prognostic factor associated with cell proliferation and migration[J].Endocr J, 2016, 63(3):287-299.
[12] KAN J Y, YEN M C, WANG J Y, et al. Nesfatin-1/Nucleobindin-2 enhances cell migration, invasion, and epithelial-mesenchymal transition via LKB1/AMPK/TORC1/ZEB1 pathways in colon cancer[J].Oncotarget, 2016, 7(21):31336-31349.

[1]	翁沛华. 超声-微泡介导miR-128通过调节PTEN抑制乳腺癌细胞阿霉素耐药[J]. 广州医药, 2021, 52(6): 35-38.
[2]	黎颂铭, 郝俊文, 洪云, 李良. 槐耳颗粒用于乳腺癌术后辅助化疗期对内分泌激素及生存期的影响[J]. 广州医药, 2021, 52(5): 109-112.
[3]	叶晔, 费伟强, 冯冠. SEER数据库中晚期三阴性乳腺癌的危险因素及预后分析[J]. 广州医药, 2021, 52(1): 26-34.
[4]	李淑怡, 黄玉珍, 蓝秀万. 乳腺癌关键基因的生物信息学分析[J]. 广州医药, 2021, 52(1): 65-71.
[5]	梁学玲, 秦艳虹. 基于网络药理学分析重用生白术组方治疗小儿功能性便秘的作用机制[J]. 广州医药, 2020, 51(5): 84-89.
[6]	黄子圣, 黄迪, 黄宇, 何志翔, 李佩霖, 翁杰锋, 李桃生, 古维立. 细胞间质液压升高对肝星状细胞的影响[J]. 广州医药, 2020, 51(5): 130-134.
[7]	王圆圆, 义勇军. 星型胶质细胞瘤预后生物标志物的筛选[J]. 广州医药, 2020, 51(4): 5-12.
[8]	谢巍, 杨妮, 肖萍. 基于网络药理学预测银杏叶治疗心肌缺血的作用机制[J]. 广州医药, 2020, 51(1): 32-38.
[9]	黄毅敏, 向炳辉, 王小锋, 岑川, 邓永康. 乳腺癌根治术中保留乳头乳晕对术后疗效、上肢功能及外观满意度的影响[J]. 广州医药, 2020, 51(1): 121-124.
[10]	欧娅, 黄耀星, 苏伟, 罗键雄, 陈伟明, 唐翔, 陈泳华, 张婷婷. 血必净注射液对SAP大鼠TLR4信号通路介导肠黏膜屏障功能障碍的影响[J]. 广州医药, 2019, 50(3): 1-5.
[11]	曹创裕, 周永健, 李瑜元. 非酒精性脂肪性肝病进展相关基因的生物信息学分析[J]. 广州医药, 2018, 49(6): 24-29.
[12]	许素真. 阿那曲唑和他莫昔芬治疗激素受体阳性绝经后转移性乳腺癌的疗效和安全性对比[J]. 广州医药, 2018, 49(6): 118-120.
[13]	魏宜霖, 柳建华, 杨毓雯. 乳腺癌超声多参数及临床病理学特点与腋窝淋巴结转移的关系[J]. 广州医药, 2018, 49(5): 89-93.
[14]	曾志坚, 陈玉兰, 邝碧茹, 练英妮, 李曙平. 6野切线射野方式用于左侧乳腺癌根治术后放疗的临床研究[J]. 广州医药, 2018, 49(4): 91-93.
[15]	王雷, 高琳璐. 乳腺癌组织中SIRT1的表达观察[J]. 广州医药, 2017, 48(4): 17-19.

基因芯片初步探讨乳腺癌转移相关蛋白Nucleobindin-2介导的信号通路

Study of breast cancer metastasis associated protein nucleobindin-2 mediated signal pathway by gene chip

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价