Department of Gynecology and Obstetrics, Nanjing Drum Tower Hospital, Clinical College of Nanjing University of Chinese Medicine, Nanjing, China.
Department of Gynecology and Obstetrics, Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine, Wenzhou, China.
J Cell Mol Med. 2024 Feb;28(4):e18081. doi: 10.1111/jcmm.18081.
Atractylodes macrocephala III (ATL III), with anti-inflammatory and antitumor effects, is the main compound of Atractylodes macrocephala. Whether ATL III has an effect on cervical cancer and the specific mechanism are still unclear. Here, we investigated the effects of ATL III on cervical cancer cells at different concentrations and found that ATL III downregulates insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3), which was found to be highly expressed in cervical cancer tissue by RNA-Seq. In this study, we found that ATL III promotes apoptosis and regulates epithelial-mesenchymal transition (EMT) in cervical cancer cells (HeLa and SiHa cells) and that IGF2BP3 is a common target gene of ATL III in HeLa and SiHa cells. The expression level of IGF2BP3 in cervical cancer cells was proportional to their migration and invasion abilities. This was verified by transfection of cells with a small interfering RNA and an IGF2BP3 overexpression plasmid. After ATL III treatment, the migration and invasion abilities of cervical cancer cells were obviously reduced, but these effects were attenuated after overexpression of IGF2BP3. In addition, the transcription factor IGF2BP3 was predicted by the JASPAR system. After intersection with our sequencing results, we verified the promotional effect of ETV5 (ETS translocation variant 5) on IGF2BP3 and found that ALT III inhibited ETV5. In general, our research showed that ATL III inhibits the migration and invasion of cervical cancer cells by regulating IGF2BP3 through ETV5.
白术 III(ATL III)具有抗炎和抗肿瘤作用,是白术的主要化合物。ATL III 是否对宫颈癌有影响以及具体机制尚不清楚。在这里,我们研究了 ATL III 在不同浓度下对宫颈癌细胞的影响,发现 ATL III 下调了 RNA-Seq 发现的宫颈癌组织中高表达的胰岛素样生长因子 2 mRNA 结合蛋白 3(IGF2BP3)。在这项研究中,我们发现 ATL III 促进了宫颈癌细胞(HeLa 和 SiHa 细胞)的凋亡并调节上皮-间充质转化(EMT),并且 IGF2BP3 是 ATL III 在 HeLa 和 SiHa 细胞中的共同靶基因。IGF2BP3 在宫颈癌细胞中的表达水平与其迁移和侵袭能力成正比。这通过用小干扰 RNA 和 IGF2BP3 过表达质粒转染细胞得到了验证。ATL III 处理后,宫颈癌细胞的迁移和侵袭能力明显降低,但过表达 IGF2BP3 后这些作用减弱。此外,通过 JASPAR 系统预测了转录因子 IGF2BP3。与我们的测序结果交叉后,我们验证了 ETV5(ETS 易位变体 5)对 IGF2BP3 的促进作用,并发现 ATL III 抑制了 ETV5。总之,我们的研究表明,ATL III 通过 ETV5 调节 IGF2BP3 抑制宫颈癌细胞的迁移和侵袭。