Abstract：
Although cytoreductive surgery followed by adjuvant chemotherapy is effective as a standard treatment for early-stage ovarian cancer, the majority of ovarian cancer cases are diagnosed at the advanced stages with dissemination to the peritoneal cavity, leading to a poor prognosis. Therefore, it is crucial to understand the cellular and molecular mechanisms underlying metastasis and identify novel therapeutic targets.
In this study, we aimed to elucidate the mechanisms underlying gene expression alterations during the acquisition of metastatic potential and characterize the metastatic subpopulations within ovarian cancer cells.
We conducted single-cell RNA sequencing of two human ovarian cancer cell lines: SKOV-3 and SKOV-3-13, a highly metastatic subclone of SKOV-3. Suppression of NFE2L1 expression was performed through siRNA-mediated knockdown and CRISPR-Cas9-mediated knockout.
Clustering and pseudotime trajectory analysis revealed pro-metastatic subpopulation within these cells. Furthermore, gene set enrichment analysis and prognosis analysis indicated that NFE2L1 could be a key transcription factor in the acquisition of metastasis potential. Inhibition of NFE2L1 significantly reduced migration and viability of both cells. In addition, NFE2L1 knockout cells exhibited significantly reduced tumor growth in a mouse xenograft model, recapitulating in silico and in vitro results.
The results presented in this study deepen our understanding of the molecular pathogenesis of ovarian cancer metastasis with the ultimate goal of developing treatments targeting pro-metastatic subclones prior to metastasis.
In this study, we aimed to elucidate the mechanisms underlying gene expression alterations during the acquisition of metastatic potential and characterize the metastatic subpopulations within ovarian cancer cells.
We conducted single-cell RNA sequencing of two human ovarian cancer cell lines: SKOV-3 and SKOV-3-13, a highly metastatic subclone of SKOV-3. Suppression of NFE2L1 expression was performed through siRNA-mediated knockdown and CRISPR-Cas9-mediated knockout.
Clustering and pseudotime trajectory analysis revealed pro-metastatic subpopulation within these cells. Furthermore, gene set enrichment analysis and prognosis analysis indicated that NFE2L1 could be a key transcription factor in the acquisition of metastasis potential. Inhibition of NFE2L1 significantly reduced migration and viability of both cells. In addition, NFE2L1 knockout cells exhibited significantly reduced tumor growth in a mouse xenograft model, recapitulating in silico and in vitro results.
The results presented in this study deepen our understanding of the molecular pathogenesis of ovarian cancer metastasis with the ultimate goal of developing treatments targeting pro-metastatic subclones prior to metastasis.
摘要：
背景：尽管细胞减灭术后辅助化疗作为早期卵巢癌的标准治疗方法是有效的，大多数卵巢癌病例在晚期被诊断为扩散到腹膜腔，导致预后不良。因此,了解转移的细胞和分子机制以及确定新的治疗靶点至关重要。
目的：在本研究中，我们旨在阐明在获得转移潜能过程中基因表达改变的潜在机制,并表征卵巢癌细胞中的转移亚群.
方法：我们对两种人卵巢癌细胞系进行了单细胞RNA测序：SKOV-3和SKOV-3-13，一种高度转移的SKOV-3亚克隆。通过siRNA介导的敲低和CRISPR-Cas9介导的敲除进行NFE2L1表达的抑制。
结果：聚类和伪时间轨迹分析揭示了这些细胞内的促转移亚群。此外，基因集富集分析和预后分析显示，NFE2L1可能是获得转移潜能的关键转录因子。NFE2L1的抑制显著降低两种细胞的迁移和活力。此外,NFE2L1敲除细胞在小鼠异种移植模型中表现出显著降低的肿瘤生长,计算机模拟和体外结果。
结论：本研究的结果加深了我们对卵巢癌转移的分子发病机制的理解，最终目标是在转移前开发针对前转移亚克隆的治疗方法。
目的：在本研究中，我们旨在阐明在获得转移潜能过程中基因表达改变的潜在机制,并表征卵巢癌细胞中的转移亚群.
方法：我们对两种人卵巢癌细胞系进行了单细胞RNA测序：SKOV-3和SKOV-3-13，一种高度转移的SKOV-3亚克隆。通过siRNA介导的敲低和CRISPR-Cas9介导的敲除进行NFE2L1表达的抑制。
结果：聚类和伪时间轨迹分析揭示了这些细胞内的促转移亚群。此外，基因集富集分析和预后分析显示，NFE2L1可能是获得转移潜能的关键转录因子。NFE2L1的抑制显著降低两种细胞的迁移和活力。此外,NFE2L1敲除细胞在小鼠异种移植模型中表现出显著降低的肿瘤生长,计算机模拟和体外结果。
结论：本研究的结果加深了我们对卵巢癌转移的分子发病机制的理解，最终目标是在转移前开发针对前转移亚克隆的治疗方法。
