PDF(Pubmed)
Abstract：
Ovarian cancer (OC) is a common and lethal gynaecological malignancy. RNA-binding proteins (RBPs) play a crucial role in governing RNA metabolism and have been implicated in the development and progression of diverse cancer types. Slight alterations in RBPs\' expression or activity can induce substantial modifications in the regulatory network. THUMPD2, as member of the RBP family, was found to have differential expression in ovarian cancer, with the mechanism has not been studied yet. In this study, THUMPD2 protein was found to be weakly expressed in the early (I + II) stages of OC (P = 0.013), with a low expression rate of 78.6 %, and highly expressed in late (III + IV) stages (P = 0.009), with a high expression rate of 84.8 %. The shRNA-mediated knockdown of THUMPD2 in OVCAR3 and SKOV3 cells resulted in increased cell proliferation but inhibited metastasis, whereas THUMPD2 overexpression had the opposite effect. THUMPD2 overexpression suppressed tumour growth in vivo. Conversely, low THUMPD2 expression promoted tumour growth. Furthermore, we identified the potential target genes and pathways of THUMPD2 using GO and KEGG analyses, which were related to the centrosome, microtubules, cell cycle, and extracellular matrix. We demonstrated that low expression of THUMPD2 in the early stage promoted tumour growth and high expression in the late stage promoted tumour metastasis. Our findings reveal the dual function of THUMPD2 in OC and suggest that THUMPD2 may serve as a therapeutic target for the treatment of OC.
摘要：
卵巢癌（OC）是一种常见且致命的妇科恶性肿瘤。RNA结合蛋白（RBP）在控制RNA代谢中起着至关重要的作用，并且与多种癌症类型的发生和发展有关。RBP表达或活性的轻微改变可诱导调控网络的实质性修饰。THUMPD2作为RBP家族的一员,被发现在卵巢癌中有差异表达，机制尚未研究。在这项研究中,发现THUMPD2蛋白在OC的早期（I+II）阶段弱表达（P=0.013），低表达率为78.6%,并在晚期（III+IV）阶段高表达（P=0.009），高表达率为84.8%。shRNA介导的THUMPD2在OVCAR3和SKOV3细胞中的敲减导致细胞增殖增加但抑制转移,而THUMPD2过表达具有相反的作用。THUMPD2过表达抑制体内肿瘤生长。相反，低THUMPD2表达促进肿瘤生长。此外，我们使用GO和KEGG分析确定了THUMPD2的潜在靶基因和通路，与中心体有关，微管，细胞周期,和细胞外基质。我们证明，早期THUMPD2的低表达促进肿瘤生长，晚期高表达促进肿瘤转移。我们的发现揭示了THUMPD2在OC中的双重功能，并表明THUMPD2可以作为OC治疗的治疗靶标。
