lncRNA SPRY4-IT1 Regulates Cell Proliferation and Migration by Sponging miR-101-3p and Regulating AMPK Expression in Gastric Cancer
lncRNA SPRY4-IT1 Regulates Cell Proliferation and Migration by Sponging miR-101-3p and Regulating AMPK Expression in Gastric Cancer
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DOI：
10.1016/j.omtn.2019.04.030
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发表时间：
2019-09-06
影响因子：
8.8
通讯作者：
Wu, Hao
中科院分区：
文献类型：
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作者：
Cao, Shuguang;Lin, Limiao;Wu, Hao
越来越多的证据表明，SPRY 4内含子转录本1（lncRNA SPRY 4-IT 1）与多种肿瘤的发生发展有关，但SPRY 4-IT 1在胃癌发生发展中的表达水平及其功能尚未见报道。我们发现SPRY 4-IT 1在胃癌中表达上调。体外实验表明，SPRY 4-IT 1基因敲低可显著抑制GC细胞增殖，导致G1期阻滞和促进凋亡，而SPRY 4-IT 1过表达可促进细胞生长。进一步的功能分析表明SPRY 4-IT 1过表达显著促进细胞迁移和侵袭。生物信息学分析提示胃癌的发生发展过程中存在SPRY 4-IT 1/miR-101- 3 p/AMPK轴。双荧光素酶报告系统验证了SPRY 4-IT 1、miR-101- 3 p和AMPK的直接相互作用。Western blot证实抑制SPRY 4-IT 1可降低AMPK的表达。此外，沉默SPRY 4-IT 1抑制体内GC生长。重要的是，我们证明SPRY 4-IT 1在来自GC患者的血清外泌体中上调，并且与癌症转移相关。总之，沉默SPRY 4-IT 1通过与miR-101- 3 p相互作用并降低抑制AMPK表达来抑制GC的进展。综上所述，我们的研究表明SPRY 4-IT 1可以作为GC患者的潜在治疗靶点。
Increasing evidence indicates that long noncoding RNA SPRY4 intronic transcript 1 (lncRNA SPRY4-IT1) has been reported to be associated with the progression of several cancers, but its expression level and the function of SPRY4-IT1 in the progression of gastric cancer (GC) have been rarely reported. Here we found that SPRY4-IT1 was upregulated in GC. In vitro experiments revealed that SPRY4-IT1 knockdown significantly inhibited GC cell proliferation by causing G1 arrest and promoting apoptosis, whereas SPRY4-IT1 overexpression promoted cell growth. Further functional assays indicated that SPRY4-IT1 overexpression significantly promoted cell migration and invasion. Bioinformatics analysis predicted that there is a SPRY4-IT1/miR-101-3p/AMPK axis in GC progression. A dual-luciferase reporter system validated the direct interaction of SPRY4-IT1, miR-101-3p, and AMPK. Western blot verified that the inhibition of SPRY4-IT1 decreased AMPK expression. Furthermore, silencing SPRY4-IT1 suppressed GC growth in vivo. Importantly, we demonstrated that SPRY4-IT1 was upregulated in serum exosomes from GC patients and correlated with cancer metastasis. Altogether, silencing SPRY4-IT1 suppresses the progression of GC by interacting with miR-101-3p and decreasing inhibiting AMPK expression. Taken together, our study demonstrates that SPRY4-IT1 could act as a potential therapeutic target for GC patients.