Department of Oncology-Pathology, Karolinska Institutet, Cancer Center Karolinska, Karolinska University Hospital, SE-171 76 Stockholm, Sweden.
Department of Medicine, Karolinska Institutet, SE-141 86 Huddinge, Sweden.
Int J Oncol. 2018 Jan;52(1):55-66. doi: 10.3892/ijo.2017.4200. Epub 2017 Nov 10.
Ovarian germ cell tumors (OGCTs) and sex cord stromal tumors (SCSTs) are rare gynecologic tumors that are derived from germ and stromal cells, respectively. Unlike their epithelial counterparts, molecular pathogenesis of these tumor types is still poorly understood. Here, we characterized microRNA (miRNA) expression profiles of 9 OGCTs (2 malignant and 7 benign) and 3 SCSTs using small RNA sequencing. We observed significant miRNA expression variations among the three tumor groups. To further demonstrate the biological relevance of our findings, we selected 12 miRNAs for validation in an extended cohort of 16 OGCTs (9 benign and 7 malignant) and 7 SCSTs by reverse transcription-quantitative polymerase chain reaction. Higher expression of miR‑373‑3p, miR‑372‑3p and miR‑302c‑3p and lower expression of miR‑199a‑5p, miR‑214‑5p and miR‑202‑3p were reproducibly observed in malignant OGCTs as compared to benign OGCTs or SCSTs. Comparing with benign OGCTs, miR‑202c‑3p and miR‑513c‑5p were more abundant in SCSTs. Additionally, we examined Beclin 1 (BECN1), a target of miR‑199a‑5p, in the clinical samples using western blot analysis. Our results show that BECN1 expression was higher in malignant OGCTs than benign OGCTs, which is concordant with their lower miR‑199a‑5p expression. This study suggests that these miRNAs may have potential value as tumor markers and implications for further understanding the molecular basis of these tumor types.
卵巢生殖细胞肿瘤(OGCT)和性索-间质肿瘤(SCST)是分别来源于生殖细胞和间质细胞的罕见妇科肿瘤。与上皮性肿瘤不同,这些肿瘤类型的分子发病机制仍知之甚少。在这里,我们使用小 RNA 测序对 9 例 OGCT(2 例恶性和 7 例良性)和 3 例 SCST 进行了 miRNA 表达谱分析。我们观察到这三组肿瘤之间存在显著的 miRNA 表达变化。为了进一步证明我们发现的生物学相关性,我们选择了 12 个 miRNA,通过逆转录定量聚合酶链反应(RT-qPCR)在 16 例 OGCT(9 例良性和 7 例恶性)和 7 例 SCST 的扩展队列中进行验证。与良性 OGCT 或 SCST 相比,恶性 OGCT 中 miR-373-3p、miR-372-3p 和 miR-302c-3p 的表达较高,miR-199a-5p、miR-214-5p 和 miR-202-3p 的表达较低。与良性 OGCT 相比,SCST 中 miR-202c-3p 和 miR-513c-5p 的表达更为丰富。此外,我们使用 Western blot 分析在临床样本中检测了 Beclin1(BECN1),这是 miR-199a-5p 的一个靶标。我们的结果表明,恶性 OGCT 中的 BECN1 表达高于良性 OGCT,这与它们较低的 miR-199a-5p 表达一致。本研究表明,这些 miRNA 可能具有作为肿瘤标志物的潜在价值,并对进一步了解这些肿瘤类型的分子基础具有启示意义。