Liu Lianqin, Li Liu, Zu Wufan, Jing Jiayu, Liu Guanjun, Sun Tingyi, Xie Qi
Department of Pathology, Henan Provincial People's Hospital; People's Hospital of Zhengzhou University; People's Hospital of Henan University, Zhengzhou, Henan, 450003, the People's Republic of China.
Department of Nursing, Henan Provincial People's Hospital; People's Hospital of Zhengzhou University; People's Hospital of Henan University, Zhengzhou, Henan, 450003, the People's Republic of China.
J Cancer. 2023 Jun 4;14(9):1648-1659. doi: 10.7150/jca.83446. eCollection 2023.
Cervical cancer (CC) is one of the leading cancers among the female reproductive system. The piwi-interacting RNA (piRNA) function and biogenesis has been studied in various cancers, including CC. But the precise mechanism of piRNA in CC is still unknown. In our study, we found that piRNA-17458 was overexpressed in CC tissues and cells. piRNA-17458 mimic and inhibitor promoted and suppressed proliferation, migration and invasion ability of CC cells, respectively. We also demonstrated that piRNA-17458 mimic could contribute to tumor growth in mice xenograft models. Besides, we also found that the piRNA-17458 mimic could enhance mRNA N6-methyladenosine(m6A) levels and increase WTAP stability in CC cells, while the effects of the mimic was reversed by the WTAP knockdown. The results of dual luciferase reporter assay showed that WTAP was a direct target of piRNA-17458. Knockdown of WTAP attenuated proliferation, migration and invasion of CC cells in piRNA-17458 mimic group. Our finding not only demonstrates for the first time that piRNA-17458 is overexpressed in CC tissues and cells, but also shows that piRNA-17458 promotes tumorigenesis of CC in a WTAP-mediated m6A methylation manner.
宫颈癌(CC)是女性生殖系统中主要的癌症之一。在包括CC在内的多种癌症中,已经对与Piwi相互作用的RNA(piRNA)的功能和生物发生进行了研究。但piRNA在CC中的精确机制仍然未知。在我们的研究中,我们发现piRNA-17458在CC组织和细胞中过表达。piRNA-17458模拟物和抑制剂分别促进和抑制CC细胞的增殖、迁移和侵袭能力。我们还证明,piRNA-17458模拟物可促进小鼠异种移植模型中的肿瘤生长。此外,我们还发现,piRNA-17458模拟物可提高CC细胞中mRNA N6-甲基腺苷(m6A)水平并增加WTAP稳定性,而WTAP敲低可逆转模拟物的作用。双荧光素酶报告基因测定结果表明,WTAP是piRNA-17458的直接靶点。敲低WTAP可减弱piRNA-17458模拟物组中CC细胞的增殖、迁移和侵袭。我们的发现不仅首次证明piRNA-17458在CC组织和细胞中过表达,还表明piRNA-17458以WTAP介导的m6A甲基化方式促进CC的肿瘤发生。