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核纤层蛋白 B2 通过介导细胞增殖和凋亡促进三阴性乳腺癌的进展。

Lamin B2 promotes the progression of triple negative breast cancer via mediating cell proliferation and apoptosis.

机构信息

Department of VIP Ward, Tianjin Medical University Cancer Institute and Hospital, Tianjin, P.R. China.

National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, P.R. China.

出版信息

Biosci Rep. 2021 Jan 29;41(1). doi: 10.1042/BSR20203874.

Abstract

Triple negative breast cancer (TNBC) is a more common type of breast cancer with high distant metastasis and poor prognosis. The potential role of lamins in cancer progression has been widely revealed. However, the function of lamin B2 (LMNB2) in TNBC progression is still unclear. The present study aimed to investigate the role of LMNB2 in TNBC. The cancer genome atlas (TCGA) database analysis and immunohistochemistry (IHC) were performed to examine LMNB2 expression levels. LMNB2 short hairpin RNA plasmid or lentivirus was used to deplete the expression of LMNB2 in human TNBC cell lines including MDA-MB-468 and MDA-MB-231. Alterations in cell proliferation and apoptosis in vitro and the nude mouse tumorigenicity assay in vivo were subsequently analyzed. The human TNBC tissues shown high expression of LMNB2 according to the bioinformation analysis and IHC assays. LMNB2 expression was correlated with the clinical pathological features of TNBC patients, including pTNM stage and lymph node metastasis. Through in vitro and in vivo assays, we confirmed LMNB2 depletion suppressed the proliferation and induced the apoptosis of TNBC cells, and inhibited tumor growth of TNBC cells in mice, with the decrease in Ki67 expression or the increase in caspase-3 expression. In conclusion, LMNB2 may promote TNBC progression and could serve as a potential therapeutic target for TNBC treatment.

摘要

三阴性乳腺癌(TNBC)是一种更为常见的乳腺癌类型,具有较高的远处转移和较差的预后。层粘连蛋白在癌症进展中的潜在作用已被广泛揭示。然而,层粘连蛋白 B2(LMNB2)在 TNBC 进展中的功能仍不清楚。本研究旨在探讨 LMNB2 在 TNBC 中的作用。通过癌症基因组图谱(TCGA)数据库分析和免疫组织化学(IHC)检测,检测了 LMNB2 的表达水平。采用 LMNB2 短发夹 RNA 质粒或慢病毒转染,在人 TNBC 细胞系 MDA-MB-468 和 MDA-MB-231 中敲低 LMNB2 的表达。随后分析了体外细胞增殖和凋亡的变化以及体内裸鼠肿瘤发生试验。根据生物信息学分析和 IHC 检测,人类 TNBC 组织显示出 LMNB2 的高表达。LMNB2 的表达与 TNBC 患者的临床病理特征相关,包括 pTNM 分期和淋巴结转移。通过体外和体内试验,我们证实了 LMNB2 耗竭抑制了 TNBC 细胞的增殖并诱导其凋亡,并且抑制了小鼠中 TNBC 细胞的肿瘤生长,Ki67 表达减少或 caspase-3 表达增加。总之,LMNB2 可能促进 TNBC 的进展,可作为 TNBC 治疗的潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f8a/7846963/d739abc941a0/bsr-41-bsr20203874-g1.jpg

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