B-cell receptor-associated protein 31 promotes migration and invasion in ovarian cancer cells

B-cell receptor-associated protein 31 promotes migration and invasion in ovarian cancer cells
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DOI:
10.3892/etm.2021.10290
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发表时间:
2021-08-01
影响因子:
2.7
通讯作者:
Ling, Bin
Ling, Bin
中科院分区:
医学4区
文献类型:
--
作者:
Liang, Haiyan;Dong, Jiqiao;Ling, Bin

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B细胞受体相关蛋白31(BAP 31)是B细胞受体的成员,其作为多种类型的新形成的蛋白质从内质网到高尔基体的转运蛋白起作用。以往的研究发现BAP 31在恶性肿瘤的发病机制中起重要作用,但其对卵巢癌的具体作用尚不清楚。本研究旨在探讨BAP 31是否影响卵巢癌及其机制。本研究采用逆转录-定量PCR、Western blotting、Cell Counting Kit-8、Transwell和免疫共沉淀(Co-IP)技术,对卵巢癌组织、人卵巢正常上皮细胞系IOSE 80和5种卵巢癌细胞系(A2780、Hey-T30、COC 1、SKOV 3和OVCAR 3)进行了转录组测序。以往的研究表明,与健康组织相比,BAP 31蛋白在各种类型的癌症组织中的表达水平显著升高,这意味着BAP 31可能在癌症的发病机制中起重要作用。目前的研究发现,BAP 31的表达在5种卵巢癌细胞系和卵巢癌组织中上调,因此BAP 31敲除[使用两种短发夹(sh)RNA质粒进行]降低了增殖、侵袭和迁移。此外,BAP 31基因敲除可通过调控N-钙粘蛋白和E-钙粘蛋白的转录调节因子TWIST 1的核聚集,在转录水平上下调N-钙粘蛋白的表达,上调E-钙粘蛋白的表达。Co-IP检测结果显示BAP 31与E-cadherin和N-cadherin之间没有相互作用,而BAP 31、E-cadherin和N-cadherin与TWIST 1蛋白之间存在相互作用。当TWIST 1在shBCAP 31细胞中过表达时,E-钙粘蛋白和N-钙粘蛋白的表达水平恢复。这些结果表明,BAP 31可以通过上皮-间质转化途径在转录水平调控卵巢癌细胞的迁移和侵袭,这可能有助于筛选卵巢癌治疗的新靶点。
B cell receptor associated protein 31 (BAP31) is a member of the B cell receptor that functions as a transporter for numerous types of newly formed proteins from the endoplasmic reticulum to the Golgi apparatus. Previous studies found that that BAP31 serves an important role in the pathogenesis of malignancy but its specific effect on ovarian cancer is not clear. The present study aimed to investigate whether BAP31 affects ovarian cancer and its underlying mechanism. In the present study, ovarian cancer tissue, human ovarian normal epithelial cell line IOSE80 and five ovarian cancer cell lines (A2780, Hey-T30, COC1, SKOV3 and OVCAR3) underwent reverse transcription-quantitative PCR, western blotting, Cell Counting Kit-8, Transwell and co-immunoprecipitation (Co-IP) assay and transcriptome sequencing. Previous studies showed that compared with healthy tissues, the expression level of BAP31 protein was found to be significantly higher in various types of cancer tissues, implying that BAP31 may serve an important role in the pathogenesis of cancer. The present study found that BAP31 expression was upregulated in five ovarian cancer cell lines and ovarian cancer tissue, such that BAP31 knockdown [performed using two short hairpin (sh)RNA plasmids] decreased proliferation, invasion and migration. In addition, BAP31 knockdown was found to downregulate the expression of N-cadherin and upregulate the expression of E-cadherin on transcriptional level by controlling the nuclear aggregation of TWIST1, a transcriptional regulator of N-cadherin and E-cadherin. There was no interaction between BAP31 and E-cadherin or N-cadherin using Co-IP detection, while BAP31, E-cadherin and N-cadherin interacted with TWIST1 protein. E-cadherin and N-cadherin expression levels recovered when TWIST1 was overexpressed in the shBCAP31 cells. These results suggest that BAP31 can regulate the migration and invasion of ovarian cancer cells through the epithelial-mesenchymal transition pathway at the transcriptional level, which may be beneficial for the identification of potentially novel targets for ovarian cancer therapy.