Huang Yan, Xu Midie, Jing Chuyu, Wu Xiaohua, Chen Xiaojun, Zhang Wei
Department of Gynecologic Oncology, Fudan University Shanghai Cancer Center, 270 Dong‑an Road, Shanghai, 200032, China.
Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
Discov Oncol. 2021 Nov 17;12(1):51. doi: 10.1007/s12672-021-00437-2.
Extracellular vesicles (EVs) play crucial roles in intercellular communication. miRNAs derived from EVs emerge as promising diagnostic indicators and therapeutic targets in a variety of malignancies. Tremendous studies have revealed the function of miRNAs derived from EVs in tumorigenesis, metastasis and other aspects. The mechanism of action of EV-derived miRNAs, however, in ovarian cancer remains largely unknown. In this study, EVs were enriched from the ovarian cancer cell lines. EVs as a whole could promote cell proliferation, invasion and new vasculature formation. However, the down-regulated EV-derived miR-320a was demonstrated to potentially suppress tumorigenesis, metastasis and angiogenesis. Moreover, EV-derived miR-320a has been proved to directly regulate a previously unknown target, ZC3H12B. An unreported role of ZC3H12B in promoting ovarian cancer cell proliferation has been elucidated and miR-320a could mediate the expression of ZC3H12B, thereby inhibiting the downstream response. As for the practical clinic values, lower expression of EV-derived miR-320a correlates with shorter survival period, indicating that EV-derived miR-320a may also serve as a prognostic biomarker in ovarian cancer. This research provides new insight into the molecular mechanism of EV-derived miR-320a in ovarian cancer and may provide new therapeutic and prognostic strategies for ovarian cancer treatment.
细胞外囊泡（EVs）在细胞间通讯中发挥着关键作用。源自EVs的微小RNA（miRNAs）在多种恶性肿瘤中成为有前景的诊断指标和治疗靶点。大量研究揭示了源自EVs的miRNAs在肿瘤发生、转移及其他方面的功能。然而，EVs衍生的miRNAs在卵巢癌中的作用机制仍 largely unknown（很大程度上未知）。在本研究中，从卵巢癌细胞系中富集了EVs。整体而言，EVs可促进细胞增殖、侵袭和新血管形成。然而，下调的源自EVs的miR - 320a被证明可能抑制肿瘤发生、转移和血管生成。此外，已证明源自EVs的miR - 320a可直接调控一个先前未知的靶点ZC3H12B。已阐明ZC3H12B在促进卵巢癌细胞增殖方面的一个未报道的作用，且miR - 320a可介导ZC3H12B的表达，从而抑制下游反应。至于实际临床价值，源自EVs的miR - 320a表达降低与生存期缩短相关，表明源自EVs的miR - 320a也可能作为卵巢癌的预后生物标志物。本研究为源自EVs的miR - 320a在卵巢癌中的分子机制提供了新见解，并可能为卵巢癌治疗提供新的治疗和预后策略。
