Department of Gastroenterology, Qilu Hospital of Shandong University (Qingdao), Qingdao, China.
Department of Otolaryngology, Qilu Hospital of Shandong University (Qingdao), Qingdao, China.
Cell Cycle. 2023 Feb;22(3):276-290. doi: 10.1080/15384101.2022.2108633. Epub 2023 Jan 1.
Esophageal cancer (EC) remains a primary cause of cancer-associated fatality worldwide and is characterized by poor prognosis. HOXA10-AS is reported to be relevant with the development of different human cancers. However, its role and regulatory mechanism in EC are still obscure. Our study targeted at investigating the functional and mechanical roles of HOXA10-AS in EC. We confirmed by RT-qPCR that HOXA10-AS presented a remarkably high expression in EC cells. Functional experiments demonstrated that knocking down HOXA10-AS weakened proliferation, invasion and migration in vitro and impeded tumorigenesis in vivo. Further, we found that HOXA10-AS positively regulated its neighbor gene HOXA10 and influenced EC cell biological activities depending on HOXA10. Mechanistically, we showed that HOXA10-AS combined with FMR1 to target and stabilize HOXA10 mRNA. Moreover, HOXA10 served as a transcriptional factor to stimulate the transcription of its target gene CHDH. Finally, rescue assays confirmed that HOXA10 influenced EC cell growth through modulating CHDH. In conclusion, our study first determines the function of HOXA10-AS in EC and demonstrates its mechanism relating to HOXA10/CHDH, suggesting HOXA10-AS as a potential novel target for EC treatment. [Figure: see text].
食管癌(EC)仍然是全球癌症相关死亡的主要原因,其预后较差。HOXA10-AS 被报道与不同人类癌症的发展有关。然而,其在 EC 中的作用和调节机制尚不清楚。我们的研究旨在探讨 HOXA10-AS 在 EC 中的功能和机械作用。我们通过 RT-qPCR 证实 HOXA10-AS 在 EC 细胞中表达显著升高。功能实验表明,敲低 HOXA10-AS 可减弱 EC 细胞的体外增殖、侵袭和迁移能力,并抑制体内肿瘤生成。此外,我们发现 HOXA10-AS 可正向调控其邻近基因 HOXA10,并依赖 HOXA10 影响 EC 细胞的生物学活性。机制上,我们表明 HOXA10-AS 与 FMR1 结合,靶向并稳定 HOXA10 mRNA。此外,HOXA10 作为转录因子,刺激其靶基因 CHDH 的转录。最后,挽救实验证实 HOXA10 通过调节 CHDH 影响 EC 细胞的生长。总之,我们的研究首次确定了 HOXA10-AS 在 EC 中的功能,并证明了其与 HOXA10/CHDH 相关的机制,提示 HOXA10-AS 可能成为 EC 治疗的一个新的潜在靶点。[图:见正文]