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GINS2調(diào)控人上皮性卵巢癌細(xì)胞增殖和凋亡

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發(fā)表時(shí)間：2024-09-06 15:13

2018年5月，四川大學(xué)華西第二醫(yī)院婦產(chǎn)科；貴州省人民醫(yī)院婦科(Department of Gynecology and Obstetrics, West China Second University Hospital, Sichuan University, Chengdu,Sichuan 610041; Departments of Gynecology, Clinical Laboratory and Pathology, Guizhou Provincial People's Hospital, Guiyang, Guizhou 550002, P.R. China) MINGRONG XI老師研究團(tuán)隊(duì)在《ONCOLOGY LETTERS》上發(fā)表論文：

“GINS2 regulates cell proliferation and apoptosis in human epithelial ovarian cancer”

“GINS2調(diào)控人上皮性卵巢癌細(xì)胞增殖和凋亡”

Abstract：

Go-Ichi-Ni-San 2 (GINS2), also known as partner of Sld five 2, is involved in the initiation of DNA replication and cell cycle progression. GINS2 is abundantly expressed in a number of malignant solid tumors, including breast cancer, melanoma and hepatic carcinoma. However, the functions of GINS2 in epithelial ovarian cancer (EOC) remain unclear. The aim of the present study was to investigate these functions. GINS2 expression was detected in EOC and normal ovarian tissues using immunohistochemistry. To investigate the functions of GINS2 in EOC, GINS2 expression was stably knocked down in SKOV-3 cells using lentiviral short hairpin RNA (shRNA). The expression of GINS2 mRNA and protein in SKOV-3 cells was examined using reverse-transcription quantitative polymerase chain reaction (RT-qPCR) and western blot analyses, respectively. Cell proliferation was determined using high-content screening and MTT assays. Cell cycle progression and apoptosis were detected using flow cytometry. Compared with normal ovarian tissues, EOC tissues expressed increased levels of GINS2 expression (16.7 vs. 58.3%). Increased expression of GINS2 mRNA was also observed in SKOV-3 and OVCAR3 cells. In the investigation of GINS2 functions in EOC, GINS2 expression at the mRNA and protein levels was significantly inhibited by specific GINS2 shRNA. GINS2 knockdown significantly inhibited the proliferation and viability of SKOV-3 cells and induced cell cycle arrest in S phase. Furthermore, GINS2 knockdown in SKOV-3 cells significantly increased cell apoptosis. GINS2 is markedly expressed in EOC tissues and cell lines. Stable GINS2 knockdown in SKOV-3 cells significantly inhibited cell proliferation and induced cell cycle arrest and cell apoptosis. Therefore, GINS2 may be involved in EOC progression.

摘要：

Go-Ichi-Ni-San 2 (GINS2)，也被稱(chēng)為Sld 5 2的伴侶，參與DNA復(fù)制的起始和細(xì)胞周期的進(jìn)展。GINS2在許多惡性實(shí)體腫瘤中大量表達(dá)，包括乳腺癌、黑色素瘤和肝癌。然而，GINS2在上皮性卵巢癌(EOC)中的功能尚不清楚。本研究的目的是研究這些功能。免疫組化檢測(cè)GINS2在EOC和正常卵巢組織中的表達(dá)。為了研究GINS2在EOC中的功能，科研人員利用慢病毒短發(fā)夾RNA (lentiviral short hairpin RNA, shRNA)穩(wěn)定地敲低了SKOV-3細(xì)胞中GINS2的表達(dá)。采用逆轉(zhuǎn)錄定量聚合酶鏈反應(yīng)(RT-qPCR)和western blot檢測(cè)GINS2 mRNA和蛋白在SKOV-3細(xì)胞中的表達(dá)。采用高含量篩選法和MTT法測(cè)定細(xì)胞增殖。流式細(xì)胞術(shù)檢測(cè)細(xì)胞周期進(jìn)展及凋亡情況。與正常卵巢組織相比，EOC組織GINS2表達(dá)水平升高(16.7%比58.3%)。SKOV-3和OVCAR3細(xì)胞中GINS2 mRNA表達(dá)增加。在對(duì)GINS2在EOC中的功能的研究中，GINS2特異性shRNA在mRNA和蛋白水平上的表達(dá)均被顯著抑制。GINS2敲低顯著抑制SKOV-3細(xì)胞的增殖和活力，誘導(dǎo)細(xì)胞周期阻滯在S期。此外，GINS2敲低SKOV-3細(xì)胞可顯著增加細(xì)胞凋亡。GINS2在EOC組織和細(xì)胞系中顯著表達(dá)。穩(wěn)定敲低GINS2可顯著抑制SKOV-3細(xì)胞增殖，誘導(dǎo)細(xì)胞周期阻滯和細(xì)胞凋亡。因此，GINS2可能參與了EOC的進(jìn)展。