Liang Haiyan, Dong Jiqiao, Cheng Ziyan, Li Qian, Feng Dingqing, Ling Bin
Department of Gynecology and Obstetrics, China-Japan Friendship Hospital, Beijing 100029, P.R. China.
GeneX Health Life Co., Ltd., Beijing 100195, P.R. China.
Exp Ther Med. 2021 Aug;22(2):858. doi: 10.3892/etm.2021.10290. Epub 2021 Jun 9.
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.
B细胞受体相关蛋白31(BAP31)是B细胞受体的成员之一,作为一种转运蛋白,负责将多种新合成的蛋白质从内质网转运至高尔基体。既往研究发现,BAP31在恶性肿瘤的发病机制中发挥重要作用,但其对卵巢癌的具体影响尚不清楚。本研究旨在探讨BAP31是否影响卵巢癌及其潜在机制。在本研究中,对卵巢癌组织、人卵巢正常上皮细胞系IOSE80和5种卵巢癌细胞系(A2780、Hey-T30、COC1、SKOV3和OVCAR3)进行了逆转录定量PCR、蛋白质印迹法、细胞计数试剂盒-8、Transwell实验、免疫共沉淀(Co-IP)实验及转录组测序。既往研究表明,与健康组织相比,BAP31蛋白在各种类型的癌组织中的表达水平显著更高,这意味着BAP31可能在癌症发病机制中发挥重要作用。本研究发现,BAP31在5种卵巢癌细胞系和卵巢癌组织中表达上调,因此,BAP31基因敲低(使用两种短发夹RNA质粒进行)可降低细胞增殖、侵袭和迁移能力。此外,通过控制N-钙黏蛋白和E-钙黏蛋白的转录调节因子TWIST1的核聚集,发现BAP31基因敲低在转录水平上可下调N-钙黏蛋白的表达并上调E-钙黏蛋白的表达。使用Co-IP检测未发现BAP31与E-钙黏蛋白或N-钙黏蛋白之间存在相互作用,而BAP31、E-钙黏蛋白和N-钙黏蛋白与TWIST1蛋白相互作用。当在shBCAP31细胞中过表达TWIST1时,E-钙黏蛋白和N-钙黏蛋白的表达水平恢复。这些结果表明,BAP31可在转录水平通过上皮-间质转化途径调节卵巢癌细胞的迁移和侵袭,这可能有助于确定卵巢癌治疗的潜在新靶点。