Department of Gynaecology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China.
Cell Transplant. 2020 Jan-Dec;29:963689720964382. doi: 10.1177/0963689720964382.
Long noncoding RNA (lncRNA) is emerging as an essential regulator in the development and progression of cancer, including cervical cancer (CC). In this study, we found a CC-related lncRNA, KCNMB2-AS1, which was significantly overexpressed in CC and linked to poor outcomes. Depletion of KCNMB2-AS1 remarkably inhibited CC cell proliferation and induced apoptosis. xenograft models revealed that knockdown of KCNMB2-AS1 evidently delayed tumor growth. Mechanistically, KCNMB2-AS1 was predominantly located in the cytoplasm and served as a competing endogenous RNA to abundantly sponge miR-130b-5p and miR-4294, resulting in the upregulation of IGF2BP3, a well-documented oncogene in CC. Moreover, IGF2BP3 was able to bind KCNMB2-AS1 by three N-methyladenosine (mA) modification sites on KCNMB2-AS1, in which IGF2BP3 acted as an mA "reader" and stabilized KCNMB2-AS1. Thus, KCNMB2-AS1 and IGF2BP3 formed a positive regulatory circuit that enlarged the tumorigenic effect of KCNMB2-AS1 in CC. Together, our data clearly suggest that KCNMB2-AS1 is a novel oncogenic mA-modified lncRNA in CC, targeting KCNMB2-AS1 and its related molecules implicate the therapeutic possibility for CC patients.
长链非编码 RNA(lncRNA)作为癌症(包括宫颈癌)发生和发展的重要调控因子正在兴起。在这项研究中,我们发现了一个与宫颈癌相关的 lncRNA,KCNMB2-AS1,它在宫颈癌中显著过表达,并与不良预后相关。KCNMB2-AS1 的耗竭显著抑制了宫颈癌细胞的增殖并诱导了细胞凋亡。异种移植模型表明,KCNMB2-AS1 的敲低明显延迟了肿瘤的生长。机制上,KCNMB2-AS1 主要位于细胞质中,作为竞争内源性 RNA 大量吸收 miR-130b-5p 和 miR-4294,导致 IGF2BP3 的上调,IGF2BP3 是宫颈癌中公认的癌基因。此外,IGF2BP3 能够通过 KCNMB2-AS1 上三个 N6-甲基腺苷(mA)修饰位点与 KCNMB2-AS1 结合,其中 IGF2BP3 作为 mA“阅读器”并稳定 KCNMB2-AS1。因此,KCNMB2-AS1 和 IGF2BP3 形成了一个正反馈调节回路,放大了 KCNMB2-AS1 在宫颈癌中的致瘤作用。总之,我们的数据清楚地表明,KCNMB2-AS1 是宫颈癌中一种新型的癌基因 mA 修饰 lncRNA,靶向 KCNMB2-AS1 及其相关分子为宫颈癌患者提供了治疗的可能性。