Sheng Jinxiu, Zhou Mingxia, Wang Chang, Jia Jinlin, Chu Jie, Ju Chenxi, Wan Junhu, He Jing, He Fucheng
Department of Medical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China; Key Clinical Laboratory of Henan Province, Zhengzhou, 450052, Henan, China.
Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China.
Exp Cell Res. 2022 Jun 1;415(1):113117. doi: 10.1016/j.yexcr.2022.113117. Epub 2022 Mar 26.
Mounting evidence suggests that long non-coding RNAs play a critical role in the occurrence and development of human malignancies. Nonetheless, it remains unknown whether Gamma-Butyrobetaine Hydroxylase 1-Antisense RNA 1 (BBOX1-AS1) participates in the regulation of esophageal squamous cell carcinoma (ESCC) carcinogenesis. Herein, we validated that BBOX1-AS1 was notably overexpressed in ESCC tissues compared to the adjacent non-tumor tissues and significantly correlated with tumor sizes. BBOX1-AS1 enhanced the malignant behavior of ESCC cells in vitro, such as cell proliferation, migration, and invasion. In addition, knockdown of BBOX1-AS1 augmented the proportion of apoptotic cells in ESCC cells. Mechanistically, BBOX1-AS1 regulated HOXB7 expression, and rescue experiments indicated that silencing of HOXB7 could abolish the malignant phenotypes mediated by BBOX1-AS1 to a certain extent. Moreover, HOXB7 participated in the activation of the Wnt/β-catenin signaling pathway. In summary, our findings substantiated that BBOX1-AS1 could activate the Wnt/β-catenin pathway by upregulating HOXB7 expression to promote ESCC progression, providing a rationale to develop novel therapeutic approaches.
越来越多的证据表明，长链非编码RNA在人类恶性肿瘤的发生和发展中起着关键作用。然而，γ-丁甜菜碱羟化酶1反义RNA 1（BBOX1-AS1）是否参与食管鳞状细胞癌（ESCC）的致癌作用仍不清楚。在此，我们证实，与相邻的非肿瘤组织相比，BBOX1-AS1在ESCC组织中显著过表达，且与肿瘤大小显著相关。BBOX1-AS1在体外增强了ESCC细胞的恶性行为，如细胞增殖、迁移和侵袭。此外，敲低BBOX1-AS1可增加ESCC细胞中凋亡细胞的比例。机制上，BBOX1-AS1调节HOXB7的表达，挽救实验表明，沉默HOXB7可在一定程度上消除由BBOX1-AS1介导的恶性表型。此外，HOXB7参与Wnt/β-连环蛋白信号通路的激活。总之，我们的研究结果证实，BBOX1-AS1可通过上调HOXB7表达激活Wnt/β-连环蛋白通路，促进ESCC进展，为开发新的治疗方法提供了理论依据。
