miR-221 and miR-222 synergistically regulate hepatocyte growth factor activator inhibitor type 1 to promote cell proliferation and migration in gastric cancer
Gastric cancer is a common malignancy with limited treatment options and poor prognosis. Introduction of novel pathways of gastric cancer will provide candidates for target therapy. Hepatocyte growth factor activator inhibitor type 1 is an integral-membrane proteinase inhibitor. Hepatocyte growth fa...
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| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2017-05-01
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| Series: | Tumor Biology |
| Online Access: | https://doi.org/10.1177/1010428317701636 |
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| author | Tao Ning Haiyang Zhang Xinyi Wang Shuang Li Le Zhang Ting Deng Likun Zhou Xia Wang Rui Liu Ming Bai Shaohua Ge Hongli Li Dingzhi Huang Guoguang Ying Yi Ba |
| author_facet | Tao Ning Haiyang Zhang Xinyi Wang Shuang Li Le Zhang Ting Deng Likun Zhou Xia Wang Rui Liu Ming Bai Shaohua Ge Hongli Li Dingzhi Huang Guoguang Ying Yi Ba |
| author_sort | Tao Ning |
| collection | DOAJ |
| description | Gastric cancer is a common malignancy with limited treatment options and poor prognosis. Introduction of novel pathways of gastric cancer will provide candidates for target therapy. Hepatocyte growth factor activator inhibitor type 1 is an integral-membrane proteinase inhibitor. Hepatocyte growth factor activator inhibitor type 1 abnormality is found in various cancers and correlates with tumor progression and metastasis. However, the mechanisms underlying the dysregulation of hepatocyte growth factor activator inhibitor type 1 expression in gastric cancer remain unclear. Although microRNAs have been reported to be involved in the development of cancer, the roles of miR-221 and miR-222 in gastric cancer have not been reported yet. In this study, we showed that hepatocyte growth factor activator inhibitor type 1 protein was downregulated, while miR-221 and miR-222 were significantly increased in gastric cancer tissues. Bioinformatic predictions and luciferase assay verified that the 3′-untranslated region of the HAI-1 gene is a direct target site for miR-221 and miR-222. Overexpression of miR-221 and miR-222 in MGC-803 cells leads to the inhibition of hepatocyte growth factor activator inhibitor type 1 protein expression, thus promoting cell proliferation and migration; whereas knockdown of miR-221 and miR-222 showed opposite effects. Moreover, we found that the expression level of hepatocyte growth factor activator protein was increased when hepatocyte growth factor activator inhibitor type 1 was knocked down in MGC-803 cells. Thus, gastric cancer is probably an autocrine tumor, and the antitumor mechanism of hepatocyte growth factor activator inhibitor type 1 in vitro might be mediated by regulating the expression of hepatocyte growth factor activator protein. Therefore, our data illustrated a novel pathway comprising miR-221and miR-222 and hepatocyte growth factor activator inhibitor type 1 in gastric cancer, which is a potential target for future clinical use. |
| format | Article |
| id | doaj-art-706245f7de3d4edf93cead1d0d5cb7be |
| institution | Kabale University |
| issn | 1423-0380 |
| language | English |
| publishDate | 2017-05-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Tumor Biology |
| spelling | doaj-art-706245f7de3d4edf93cead1d0d5cb7be2025-08-20T03:56:13ZengSAGE PublishingTumor Biology1423-03802017-05-013910.1177/1010428317701636miR-221 and miR-222 synergistically regulate hepatocyte growth factor activator inhibitor type 1 to promote cell proliferation and migration in gastric cancerTao NingHaiyang ZhangXinyi WangShuang LiLe ZhangTing DengLikun ZhouXia WangRui LiuMing BaiShaohua GeHongli LiDingzhi HuangGuoguang YingYi BaGastric cancer is a common malignancy with limited treatment options and poor prognosis. Introduction of novel pathways of gastric cancer will provide candidates for target therapy. Hepatocyte growth factor activator inhibitor type 1 is an integral-membrane proteinase inhibitor. Hepatocyte growth factor activator inhibitor type 1 abnormality is found in various cancers and correlates with tumor progression and metastasis. However, the mechanisms underlying the dysregulation of hepatocyte growth factor activator inhibitor type 1 expression in gastric cancer remain unclear. Although microRNAs have been reported to be involved in the development of cancer, the roles of miR-221 and miR-222 in gastric cancer have not been reported yet. In this study, we showed that hepatocyte growth factor activator inhibitor type 1 protein was downregulated, while miR-221 and miR-222 were significantly increased in gastric cancer tissues. Bioinformatic predictions and luciferase assay verified that the 3′-untranslated region of the HAI-1 gene is a direct target site for miR-221 and miR-222. Overexpression of miR-221 and miR-222 in MGC-803 cells leads to the inhibition of hepatocyte growth factor activator inhibitor type 1 protein expression, thus promoting cell proliferation and migration; whereas knockdown of miR-221 and miR-222 showed opposite effects. Moreover, we found that the expression level of hepatocyte growth factor activator protein was increased when hepatocyte growth factor activator inhibitor type 1 was knocked down in MGC-803 cells. Thus, gastric cancer is probably an autocrine tumor, and the antitumor mechanism of hepatocyte growth factor activator inhibitor type 1 in vitro might be mediated by regulating the expression of hepatocyte growth factor activator protein. Therefore, our data illustrated a novel pathway comprising miR-221and miR-222 and hepatocyte growth factor activator inhibitor type 1 in gastric cancer, which is a potential target for future clinical use.https://doi.org/10.1177/1010428317701636 |
| spellingShingle | Tao Ning Haiyang Zhang Xinyi Wang Shuang Li Le Zhang Ting Deng Likun Zhou Xia Wang Rui Liu Ming Bai Shaohua Ge Hongli Li Dingzhi Huang Guoguang Ying Yi Ba miR-221 and miR-222 synergistically regulate hepatocyte growth factor activator inhibitor type 1 to promote cell proliferation and migration in gastric cancer Tumor Biology |
| title | miR-221 and miR-222 synergistically regulate hepatocyte growth factor activator inhibitor type 1 to promote cell proliferation and migration in gastric cancer |
| title_full | miR-221 and miR-222 synergistically regulate hepatocyte growth factor activator inhibitor type 1 to promote cell proliferation and migration in gastric cancer |
| title_fullStr | miR-221 and miR-222 synergistically regulate hepatocyte growth factor activator inhibitor type 1 to promote cell proliferation and migration in gastric cancer |
| title_full_unstemmed | miR-221 and miR-222 synergistically regulate hepatocyte growth factor activator inhibitor type 1 to promote cell proliferation and migration in gastric cancer |
| title_short | miR-221 and miR-222 synergistically regulate hepatocyte growth factor activator inhibitor type 1 to promote cell proliferation and migration in gastric cancer |
| title_sort | mir 221 and mir 222 synergistically regulate hepatocyte growth factor activator inhibitor type 1 to promote cell proliferation and migration in gastric cancer |
| url | https://doi.org/10.1177/1010428317701636 |
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