MicroRNA-320 inhibits invasion and induces apoptosis by targeting CRKL and inhibiting ERK and AKT signaling in gastric cancer cells.
MicroRNA-320 inhibits invasion and induces apoptosis by targeting CRKL and inhibiting ERK and AKT signaling in gastric cancer cells.
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DOI：
10.2147/ott.s123324
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发表时间：
2017
影响因子：
4
通讯作者：
Wang E
中科院分区：
文献类型：
--
作者：
Zhao Y;Dong Q;Wang E
在几种人类癌症中已经报道了microRNA-320（miR-320）下调。到目前为止，其表达模式和在人类癌症中的生物学作用仍然未知。本研究旨在阐明其在胃癌中的临床表达模式及其生物学功能。我们发现miR-320在胃癌组织中表达下调。将miR-320模拟物转染到具有低内源性表达的SGC-7901细胞中。miR-320抑制剂用于内源性高表达的BGC-823细胞。我们发现miR-320抑制了SGC-7901的增殖和侵袭，并在mRNA和蛋白水平上降低了cyclin D1和MMP 9的表达。我们还发现，miR-320模拟下调化疗耐药性和细胞生存的胃癌细胞时，用5-氟尿嘧啶处理。miR-320抑制剂在BGC-823细胞株中表现出相反的作用。此外，我们还发现miR-320模拟物能够抑制AKT和ERK的活性。通过荧光素酶报告基因检测，我们发现CRKL是miR-320的靶点。miR-320模拟下调CRKL表达，而miR-320抑制剂上调CRKL表达。miR-320抑制SGC-7901细胞中CRKL-3′-非翻译区报告基因强度。此外，CRKL消耗消除了miR-320的作用。在胃癌组织中，我们观察到CRKL和miR-320之间呈负相关。结论：miR-320表达下调与胃癌的恶性进展密切相关。miR-320通过靶向CRKL通过ERK和AKT信号传导抑制增殖、侵袭和化学抗性。
MicroRNA-320 (miR-320) downregulation has been reported in several human cancers. Until now, its expression pattern and biological roles in human cancer remain unknown. This study aims to clarify its clinical expression pattern and biological function in gastric cancers. We found miR-320 level was downregulated in gastric cancer tissues. miR-320 mimic was transfected in SGC-7901 cells with low endogenous expression. miR-320 inhibitor was used in BGC-823 cells with high endogenous expression. We found that miR-320 inhibited SGC-7901 proliferation and invasion, with decreased expression of cyclin D1 and MMP9 at both mRNA and protein levels. We also found that miR-320 mimic downregulated chemoresistance and cell survival of gastric cancer cells when treated with 5-fluorouracil. miR-320 inhibitor displayed the opposite effects in BGC-823 cell line. In addition, we discovered that miR-320 mimic could inhibit AKT and ERK activity. By using luciferase reporter assay, we found that CRKL serves as the target of miR-320. miR-320 mimic downregulated CRKL expression, whereas miR-320 inhibitor upregulated CRKL expression. miR-320 suppressed CRKL-3′-untranslated region reporter intensity in SGC-7901 cells. Furthermore, CRKL depletion abrogated the effects of miR-320. In gastric cancer tissues, we observed a negative correlation between CRKL and miR-320. In conclusion, our study demonstrated that downregulation of miR-320 was closely related with malignant progression of gastric cancer. miR-320 inhibits proliferation, invasion, and chemoresistance through ERK and AKT signaling by targeting CRKL.