Hua Minhui, Chen Yujie, Jia Meiqun, Lv Wenxuan, Xu Yunzhao, Zhang Yuquan
Suzhou Medical College of Soochow University, Suzhou, 215123, China.
Department of Gynecology and Obstetrics, Affiliated Hospital of Nantong University, Nantong, 226001, China.
Heliyon. 2024 Jun 25;10(13):e33201. doi: 10.1016/j.heliyon.2024.e33201. eCollection 2024 Jul 15.
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.
卵巢癌（OC）是一种常见且致命的妇科恶性肿瘤。RNA结合蛋白（RBPs）在调控RNA代谢中起关键作用，并与多种癌症类型的发生和发展有关。RBPs表达或活性的微小改变可导致调控网络发生重大变化。THUMPD2作为RBP家族的成员，在卵巢癌中存在差异表达，但其机制尚未得到研究。在本研究中，发现THUMPD2蛋白在OC的早期（I + II）阶段表达较弱（P = 0.013），低表达率为78.6%，而在晚期（III + IV）阶段高表达（P = 0.009），高表达率为84.8%。在OVCAR3和SKOV3细胞中，通过shRNA介导敲低THUMPD2导致细胞增殖增加但转移受到抑制，而THUMPD2过表达则产生相反的效果。THUMPD2过表达在体内抑制肿瘤生长。相反，THUMPD2低表达促进肿瘤生长。此外，我们使用GO和KEGG分析确定了THUMPD2的潜在靶基因和途径，这些基因和途径与中心体、微管、细胞周期和细胞外基质有关。我们证明，THUMPD2在早期低表达促进肿瘤生长，在晚期高表达促进肿瘤转移。我们的研究结果揭示了THUMPD2在OC中的双重功能，并表明THUMPD2可能作为OC治疗的一个治疗靶点。
