Long non‑coding RNA H19 regulates cell growth and metastasis via the miR‑22‑3p/Snail1 axis in gastric cancer

下调和上调 癌症研究 癌基因 转移 长非编码RNA 生物 细胞生长 基因敲除 癌症 细胞周期 上皮-间质转换 细胞 细胞凋亡 基因 遗传学 生物化学
作者
Li Gan,Lin Lv,Shengtao Liao
出处
期刊:International Journal of Oncology [Spandidos Publishing]
被引量:71
标识
DOI:10.3892/ijo.2019.4773
摘要

Gastric cancer (GC) is the fifth most prevalent type of malignancy and the third leading cause of cancer‑related mortality worldwide, with the prognosis of patients with late‑stage GC remaining at poor levels. Long non‑coding RNA (lncRNA) H19 (H19) is involved in the growth and metastasis of tumors, and it is upregulated under hypoxic conditions and in certain types of cancer; however, the underlying mechanisms of action of this lncRNA as regards the initiation and development of GC remain unknown. Thus, in the present study, we aimed to determine the role of lncRNA H19 in GC and to elucidate the underlying mechanisms. H19 was found to be upregulated in GC tissues and cells compared with the para‑cancerous tissues, and an elevated expression of H19 was associated with lymph node metastasis and TNM stage. Furthermore, the downregulation of H19 suppressed the proliferation, invasion, migration and epithelial‑mesenchymal transition of GC cells in vitro and suppressed tumor growth in vivo. H19 was also found to be able to bind with miR‑22‑3p, and H19‑induced cell growth and metastasis were shown to be reversed by the upregulation of miR‑22‑3p; the miR‑22‑3p level was found to inversely correlate with H19 expression in GC tissues. Furthermore, the overexpression of miR‑22‑3p notably suppressed the proliferation, migration and invasion of GC cells, and these effects were enhanced by the downregulation of Snail1. In addition, cell growth and metastasis induced by miR‑22‑3p downregulation were partially reversed by the knockdown of Snail1. Furthermore, a negative correlation was observed between the mRNA expression levels of miR‑22‑3p and Snail1 in GC tissues. On the whole, the findings of the present study revealed that H19 was upregulated in GC tissues, which promoted tumor growth and metastasis via the miR‑22‑3p/Snail1 signaling pathway. In summary, these findings provide novel insight into the potential regulatory roles of H19 in GC, and suggest that the H19/miR‑22‑3p/Snail1 axis may prove to be a promising therapeutic target for the treatment of patients with GC.

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