Department of Gastroenterology, Shengli Oilfield Central Hospital, Dongying, P.R. China.
Oncol Res. 2018 Sep 14;26(8):1285-1294. doi: 10.3727/096504018X15166193231711. Epub 2018 Jan 31.
Long noncoding RNA (lncRNA) growth arrest-specific transcript 5 (GAS5) has been revealed to be associated with the progression of various cancers. However, the biological roles of GAS5 in esophageal cancer (EC) remain unclear. We aimed to thoroughly explore the functions of GAS5 in EC. The results showed that GAS5 expression was increased in EC cells (ECA109, TE-1, TE-3, and EC9706) compared to SHEE cells. Knockdown of GAS5 decreased cell viability, migration, and invasion and induced apoptosis in EC9706 cells. Moreover, miR-301a appeared to be directly sponged by GAS5, and miR-301a suppression obviously alleviated the protumor effects of GAS5. Furthermore, miR-301a positively regulated CXCR4 expression, and overexpression of CXCR4 induced apoptosis and abolished the promoting effect of miR-301a inhibition on cell viability, migration, and invasion. Besides, miR-301a blocked Wnt/β-catenin and NF-κB signaling pathways by regulation of CXCR4. Our results indicated that GAS5 promoted proliferation and metastasis and inhibited apoptosis by regulation of miR-301a in EC. These data contributed to our understanding of the mechanisms of miRNA-lncRNA interaction and provides a novel therapeutic strategy for EC.
长链非编码 RNA（lncRNA）生长停滞特异性转录物 5（GAS5）已被证明与多种癌症的进展有关。然而，GAS5 在食管癌（EC）中的生物学作用仍不清楚。我们旨在深入探讨 GAS5 在 EC 中的功能。结果表明，与 SHEE 细胞相比，EC 细胞（ECA109、TE-1、TE-3 和 EC9706）中 GAS5 的表达增加。GAS5 敲低降低了 EC9706 细胞的活力、迁移和侵袭，并诱导了细胞凋亡。此外，miR-301a 似乎被 GAS5 直接吸收，而 miR-301a 的抑制明显减轻了 GAS5 的促肿瘤作用。此外，miR-301a 正向调节 CXCR4 的表达，过表达 CXCR4 诱导细胞凋亡，并消除了 miR-301a 抑制对细胞活力、迁移和侵袭的促进作用。此外，miR-301a 通过调节 CXCR4 阻断了 Wnt/β-catenin 和 NF-κB 信号通路。我们的结果表明，GAS5 通过调节 miR-301a 在 EC 中促进增殖和转移，抑制凋亡。这些数据有助于我们理解 miRNA-lncRNA 相互作用的机制，并为 EC 提供了一种新的治疗策略。
