Chang Xiaohan, Zhang Huijie, Yang Qing, Pang Li
Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University , Shenyang, People's Republic of China.
Cell Cycle. 2020 Jun;19(11):1391-1403. doi: 10.1080/15384101.2020.1750812. Epub 2020 Apr 14.
Long non-coding RNA (lncRNA) SOX2 overlapping transcript (SOX2OT) has been shown to play an oncogenic role in diverse cancers, generating eight transcript variants. SOX2 is located in the third intron of SOX2OT. However, the biological function of SOX2OT in cervical cancer and implication with SOX2 remain to be further explored. In this study, we screened the expression pattern of different SOX2OT transcript variants in cervical cancer cells. Interestingly, both high-expression levels of SOX2OT transcript 7 (SOX2OT-7) and SOX2 were detected in C-33A (HPV) and SiHa (HPV16) cells. Thus, C-33A and SiHa cells were conducted to investigate the effects of SOX2OT on cell growth, migration and invasion. Finally, rescue experiments were performed to confirm the role of SOX2 in SOX2OT-mediated regulation of cervical cancer progression. The results showed that knockdown of SOX2OT suppressed cell viability, arrested cell cycle and ameliorated migration and invasion ability of C-33A and SiHa cells. Ectopic expression of SOX2OT-7 exacerbated cervical cancer cell proliferation, migration and invasion. In addition, we found that the expression levels and protein stability of SOX2 were positively regulated by SOX2OT. Inhibition of SOX2 could block the malignant phenotypes of C-33A and SiHa cells by SOX2OT-7. In conclusion, these findings indicate that lncRNA SOX2OT contributes to the growth, migration and invasion of cervical cancer cells by modulating SOX2. Importantly, we demonstrate that the transcript SOX2OT-7 may be a novel and promising biomarker for both HPV and HPV16 cervical cancer.
长链非编码RNA（lncRNA）SOX2重叠转录本（SOX2OT）已被证明在多种癌症中发挥致癌作用，可产生8种转录变体。SOX2位于SOX2OT的第三个内含子中。然而，SOX2OT在宫颈癌中的生物学功能及其与SOX2的关系仍有待进一步探索。在本研究中，我们筛选了不同SOX2OT转录变体在宫颈癌细胞中的表达模式。有趣的是，在C-33A（HPV）和SiHa（HPV16）细胞中均检测到SOX2OT转录本7（SOX2OT-7）和SOX2的高表达水平。因此，利用C-33A和SiHa细胞研究了SOX2OT对细胞生长、迁移和侵袭的影响。最后，进行了拯救实验以证实SOX2在SOX2OT介导的宫颈癌进展调控中的作用。结果表明，敲低SOX2OT可抑制C-33A和SiHa细胞的活力，使细胞周期停滞，并改善其迁移和侵袭能力。SOX2OT-7的异位表达加剧了宫颈癌细胞的增殖、迁移和侵袭。此外，我们发现SOX2OT正向调节SOX2的表达水平和蛋白质稳定性。抑制SOX2可阻断SOX2OT-7诱导的C-33A和SiHa细胞的恶性表型。总之，这些发现表明lncRNA SOX2OT通过调节SOX2促进宫颈癌细胞的生长、迁移和侵袭。重要的是，我们证明转录本SOX2OT-7可能是HPV和HPV16宫颈癌的一种新型且有前景的生物标志物。
