Long non-coding RNA GAS5 inhibits ovarian cancer cell proliferation via the control of microRNA-21 and SPRY2 expression.
Long non-coding RNA GAS5 inhibits ovarian cancer cell proliferation via the control of microRNA-21 and SPRY2 expression.
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长期非编码RNA GAS5通过控制microRNA-21和SPRY2表达抑制卵巢癌细胞的增殖。
DOI：
10.3892/etm.2018.6188
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发表时间：
2018-07
影响因子：
2.7
通讯作者：
Wang S
中科院分区：
文献类型：
--
作者：
Ma N;Li S;Zhang Q;Wang H;Qin H;Wang S
近几十年来，许多长非编码（lnc）RNA，包括生长停滞特异性转录本5（GAS 5），已被证明在人类癌症中发挥促进或抑制作用。据报道，lncRNA GAS 5的表达减少促进细胞增殖、迁移和侵袭，并指示卵巢癌的不良预后。然而，GAS 5参与卵巢癌生长的确切潜在分子机制仍然未知。本研究旨在探讨GAS 5对卵巢癌细胞增殖的调控机制。定量聚合酶链反应和蛋白质印迹分析分别用于检查RNA和蛋白质表达。MTT法检测细胞增殖情况。进行荧光素酶报告基因测定以验证靶向关系。结果表明，与癌旁组织和正常卵巢上皮细胞相比，卵巢癌组织和细胞系中GAS 5和SPRY 2的表达水平显著下调，而microRNA（miR）-21的表达水平显著上调。GAS 5表达下调与临床分期的进展显著相关。荧光素酶分析数据表明，miR-21是GAS 5的直接靶点，SPRY 2是卵巢癌来源的A2780细胞中miR-21的靶基因。GAS 5过表达可显著抑制卵巢癌细胞的增殖，并伴有miR-21的下调和SPRY 2的上调。miR-21的过表达导致A2780细胞增殖显著降低，这伴随着SPRY 2表达的降低。此外，miR-21过表达减弱了GAS 5对A2780细胞增殖的抑制作用，并恢复了GAS 5对SPRY 2表达的促进作用。此外，SPRY 2的敲低也挽救了GAS 5对A2780细胞增殖的抑制作用。总之，我们的研究表明，GAS 5对卵巢癌细胞的增殖发挥抑制作用，至少部分通过抑制miR-21表达和随后增加SPRY 2表达。这些发现表明，GAS 5/miR-21/SPRY 2信号通路可能是卵巢癌的潜在治疗靶点。
In recent decades, numerous long non-coding (lnc)RNAs, including growth arrest-specific transcript 5 (GAS5), have been demonstrated to exert promoting or suppressive effects in human cancers. Decreased expression of the lncRNA GAS5 was reported to promote cell proliferation, migration and invasion and indicate poor prognosis in ovarian cancer. However, the exact underlying molecular mechanism through which GAS5 is involved in ovarian cancer growth remains unknown. The present study aimed to investigate the regulatory mechanism of GAS5 in ovarian cancer cell proliferation. Quantitative polymerase chain reaction and western blot analysis were used to examine RNA and protein expression, respectively. An MTT assay was used to examine cell proliferation. A luciferase reporter gene assay was conducted to verify the targeting relationship. It was identified that the expression levels of GAS5 and Sprouty homolog 2 (SPRY2) were significantly downregulated, while the expression level of microRNA (miR)-21 was significantly upregulated in ovarian cancer tissues and cell lines compared with adjacent non-tumor tissues and normal ovarian epithelial cells, respectively. Downregulation of GAS5 was significantly associated with advanced clinical stage. Luciferase assay data indicated that miR-21 was a direct target of GAS5 and that SPRY2 was a target gene of miR-21 in ovarian cancer-derived A2780 cells. GAS5 overexpression significantly inhibited the proliferation of ovarian cancer cells, which was accompanied by the downregulation of miR-21 and the upregulation of SPRY2. The overexpression of miR-21 caused a significant decrease in A2780 cell proliferation, which was accompanied by reduced SPRY2 expression. Furthermore, miR-21 overexpression attenuated the suppressive effects of GAS5 on A2780 cell proliferation and rescued the promoting effects of GAS5 on SPRY2 expression. In addition, the knockdown of SPRY2 also rescued the suppressive effects of GAS5 on the proliferation of A2780 cells. In summary, our study demonstrates that GAS5 exerts a suppressive effect on the proliferation of ovarian cancer cells, at least in part via the inhibition of miR-21 expression and subsequent increased SPRY2 expression. These findings suggest that the GAS5/miR-21/SPRY2 signaling pathway may be a potential therapeutic target in ovarian cancer.
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