Department of Obstetrics and Gynecology, Ningbo Women and Children's Hospital, Ningbo, 315000, Zhejiang, China.
Department of Gynecological Pelvic Floor and Oncology, Chongqing Health Center for Women and Children, Chongqing, 401120, China.
Reprod Sci. 2021 Oct;28(10):3000-3009. doi: 10.1007/s43032-021-00626-y. Epub 2021 Jun 2.
Long non-coding RNAs (lncRNAs) are crucial participants in cancer development. HOXA cluster antisense RNA 2 (HOXA-AS2) plays a tumor promoter role in bladder cancer. However, the functional role of HOXA-AS2 in cervical cancer remains unclear. Our study first found that HOXA-AS2 expression was up-regulated in cervical cancer cells. Then functional analysis including cell counting kit-8 (CCK-8), colony formation, transwell, and wound healing uncovered that reduction of HOXA-AS2 remarkably impeded cell proliferation and migration in cervical cancer. Additionally, luciferase reporter assays were performed to confirm that HOXA-AS2 activated Notch signaling pathway via the mediation of independent recombination signal binding protein for JK (RBP-JK) activity. As we know, Notch intracellular domain (NICD) is associated with RBP-JK in the nucleus to promote target genes in the Notch pathway. Through RNA immunoprecipitation (RIP), RNA pull down, and fluorescent in situ hybridization (FISH) assays, we observed that HOXA-AS2 combined with NICD. Moreover, the data from Co-IP assays indicated that HOXA-AS2 reduction weakened the interaction of NICD and RBP-JK. Collectively, HOXA-AS2 played a cancer-promoting role in cervical cancer development by modulating the Notch pathway, which might become a novel target for cervical cancer treatment.
长链非编码 RNA（lncRNA）是癌症发展的关键参与者。HOXA 簇反义 RNA 2（HOXA-AS2）在膀胱癌中发挥肿瘤促进作用。然而，HOXA-AS2 在宫颈癌中的功能作用尚不清楚。我们的研究首先发现 HOXA-AS2 在宫颈癌细胞中表达上调。然后进行的功能分析，包括细胞计数试剂盒-8（CCK-8）、集落形成、Transwell 和划痕愈合实验表明，降低 HOXA-AS2 可显著抑制宫颈癌细胞的增殖和迁移。此外，进行了荧光素酶报告基因实验以证实 HOXA-AS2 通过独立重组信号结合蛋白 JK（RBP-JK）活性介导激活 Notch 信号通路。众所周知，Notch 细胞内结构域（NICD）与核内的 RBP-JK 结合以促进 Notch 通路中的靶基因。通过 RNA 免疫沉淀（RIP）、RNA 下拉和荧光原位杂交（FISH）实验，我们观察到 HOXA-AS2 与 NICD 结合。此外，Co-IP 实验数据表明，降低 HOXA-AS2 减弱了 NICD 和 RBP-JK 的相互作用。综上所述，HOXA-AS2 通过调节 Notch 通路在宫颈癌发展中发挥促癌作用，这可能成为宫颈癌治疗的新靶点。
