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长链非编码RNA BM466146的过表达预示着乳腺癌更好的预后。

Overexpression of LncRNA BM466146 Predicts Better Prognosis of Breast Cancer.

作者信息

Zhang Yunxiang, Dong Xiaotong, Wang Yang, Wang Liquan, Han Guiyan, Jin Lvcheng, Fan Yanping, Xu Guodong, Yuan Dawei, Zheng Jie, Guo Xiangyu, Gao Peng

机构信息

Key Laboratory for Experimental Teratology of the Ministry of Education, Department of Pathology, School of Basic Medical Sciences, Shandong University, Jinan, China.

Pathology Department, First Affiliated Hospital of Weifang Medical University, (Weifang People's Hospital), Weifang, China.

出版信息

Front Oncol. 2021 Jan 29;10:628757. doi: 10.3389/fonc.2020.628757. eCollection 2020.

Abstract

This study analyzes the expression and clinical significance of long non-coding RNA (lncRNA) BM466146 in breast cancer, and explores the role of BM466146 in immune regulation. The expression of BM466146 in 89 cases of breast cancer and their corresponding non-cancerous breast tissues was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Kaplan-Meier survival analysis was applied to evaluate patient survival. EDU and CCK-8 experiments on breast cancer cells were performed to verify the function of BM466146 . The target genes of BM466146 were screened by informatics analysis to predict associated miRNAs and their corresponding mRNAs, immune genes associated with lncRNAs and chemokines associated with CD8. Immunohistochemistry was used to detect the expression of CD8, Ki-67, and CXCL-13 in the 89 breast cancer tissues. It was found that the expression of lncRNA BM466146 in breast cancer tissues was significantly lower than that in normal breast tissues ( < 0.001). In breast cancer, tissues that overexpressed BM466146 exhibited a lower Ki-67 index compared with that of low BM466146 expression ( = 0.048). Kaplan-Meier survival analysis showed that breast cancer patients with overexpression of BM466146 had longer overall survival. EDU and CCK8 experiments showed that overexpression of BM466146 inhibited the proliferation of breast cancer cells. The hsa-miR-224-3p is associated with BM466146, and its target gene might be CXCL-13. The positive CD8 cells in the BM466146 overexpression group was higher than that in the low BM466146 expression group (=0.027), and the positive CD8 cells in the CXCL-13 positive group was higher (=0.023) than that of the negative group. Our results indicate that the lncRNA BM466146 has the function of tumor suppressor gene. Overexpression of BM466146 is associated with better prognosis. BM466146 could regulate CXCL-13 by adsorbing hsa-miR-224-3p and inducing CD8 T cells to accumulate in the tumor area which regulate immune response. Therefore, BM466146 could be a prognostic biomarker and a molecular immune target of breast cancer.

摘要

本研究分析长链非编码RNA(lncRNA)BM466146在乳腺癌中的表达及临床意义,并探讨BM466146在免疫调节中的作用。采用定量实时聚合酶链反应(qRT-PCR)检测89例乳腺癌组织及其相应癌旁乳腺组织中BM466146的表达。应用Kaplan-Meier生存分析评估患者生存情况。对乳腺癌细胞进行5-乙炔基-2'-脱氧尿苷(EDU)和细胞计数试剂盒-8(CCK-8)实验以验证BM466146的功能。通过信息学分析筛选BM466146的靶基因,预测相关的微小RNA(miRNA)及其相应的信使核糖核酸(mRNA)、与lncRNA相关的免疫基因以及与CD8相关的趋化因子。采用免疫组织化学法检测89例乳腺癌组织中CD8、Ki-67和CXC趋化因子配体13(CXCL-13)的表达。结果发现,lncRNA BM466146在乳腺癌组织中的表达明显低于正常乳腺组织(<0.001)。在乳腺癌中,与BM466146低表达组织相比,BM466146过表达组织的Ki-67指数较低(=0.048)。Kaplan-Meier生存分析显示,BM466146过表达的乳腺癌患者总生存期更长。EDU和CCK8实验表明,BM466146过表达抑制乳腺癌细胞增殖。hsa-miR-224-3p与BM466146相关,其靶基因可能是CXCL-13。BM466146过表达组的CD8阳性细胞高于BM466146低表达组(=0.027),CXCL-13阳性组的CD8阳性细胞高于阴性组(=0.023)。我们的结果表明,lncRNA BM466146具有肿瘤抑制基因的功能。BM466146过表达与较好的预后相关。BM466146可通过吸附hsa-miR-224-3p并诱导CD8 T细胞在肿瘤区域积聚来调节CXCL-13,从而调节免疫反应。因此,BM466146可能是乳腺癌的一个预后生物标志物和分子免疫靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b20/7878538/8f78df21145c/fonc-10-628757-g001.jpg

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