INPP4B promotes colorectal cancer cell proliferation by activating mTORC1 signaling and cap-dependent translation
Xin-Hua Ruan,1,* Xi-Mei Liu,1,* Zhi-Xiang Yang,1,* Shao-Peng Zhang,1,* Quan-Zheng Li,1 Chun-Sheng Lin2 1Department of Cardiac Surgery, TianJin Union Medical Centre, Tianjin, People’s Republic of China; 2Department of Medical Service, TianJin Union Medical Centre, Tianjin, People&rsquo...
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doaj-0905acfb563a484d96c776365b2bdf0a2020-11-24T20:49:14ZengDove Medical PressOncoTargets and Therapy1178-69302019-04-01Volume 123109311745256INPP4B promotes colorectal cancer cell proliferation by activating mTORC1 signaling and cap-dependent translationRuan XLiu XYang ZZhang SLi QLin CXin-Hua Ruan,1,* Xi-Mei Liu,1,* Zhi-Xiang Yang,1,* Shao-Peng Zhang,1,* Quan-Zheng Li,1 Chun-Sheng Lin2 1Department of Cardiac Surgery, TianJin Union Medical Centre, Tianjin, People’s Republic of China; 2Department of Medical Service, TianJin Union Medical Centre, Tianjin, People’s Republic of China *These authors contributed equally to this work Background and objective: Inositol polyphosphate 4-phosphatase type II (INPP4B) is overexpressed in CRC tissues, and emerges as an oncogene. However, the mechanism by which INPP4B regulates CRC cell proliferation remains largely unclear. In this study, we aimed to investigate the regulatory mechanisms of INPP4B in CRC. Materials and methods: The expression levels of mRNA were detected by qRT-PCR. The expression levels of protein were determined by Western blot. Cell Counting Kit-8 (CCK-8) assays and BrdU incorporation assays were performed to evaluate cell proliferation abilities. Bicistronic luciferase assays and the m7GTP pull down assay were performed to measure the cap-dependent translation in cells. Results: INPP4B promotes CRC cell proliferation by increasing mTORC1 activity. Furthermore, it was shown that the activation of mTORC1 signaling by INPP4B led to increased cap-dependent translation, which is essential for INPP4B-mediated CRC cell proliferation. Finally, it was demonstrated that increased AKT and serum and glucocorticoid-inducible kinase 1 activity contributed to the activation of cap-dependent translation induced by INPP4B. Conclusion: Collectively, the present study reveals INPP4B promotes colorectal cancer cell proliferation by activating mTORC1 signaling and cap-dependent translation. Keywords: colorectal cancer, INPP4B, mTORC1, 4E-BP1, cap-dependent translationhttps://www.dovepress.com/inpp4b-promotes-colorectal-cancer-cell-proliferation-by-activating-mto-peer-reviewed-article-OTTColorectal cancerINPP4BmTORC14E-BP1cap-dependent translation |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ruan X Liu X Yang Z Zhang S Li Q Lin C |
spellingShingle |
Ruan X Liu X Yang Z Zhang S Li Q Lin C INPP4B promotes colorectal cancer cell proliferation by activating mTORC1 signaling and cap-dependent translation OncoTargets and Therapy Colorectal cancer INPP4B mTORC1 4E-BP1 cap-dependent translation |
author_facet |
Ruan X Liu X Yang Z Zhang S Li Q Lin C |
author_sort |
Ruan X |
title |
INPP4B promotes colorectal cancer cell proliferation by activating mTORC1 signaling and cap-dependent translation |
title_short |
INPP4B promotes colorectal cancer cell proliferation by activating mTORC1 signaling and cap-dependent translation |
title_full |
INPP4B promotes colorectal cancer cell proliferation by activating mTORC1 signaling and cap-dependent translation |
title_fullStr |
INPP4B promotes colorectal cancer cell proliferation by activating mTORC1 signaling and cap-dependent translation |
title_full_unstemmed |
INPP4B promotes colorectal cancer cell proliferation by activating mTORC1 signaling and cap-dependent translation |
title_sort |
inpp4b promotes colorectal cancer cell proliferation by activating mtorc1 signaling and cap-dependent translation |
publisher |
Dove Medical Press |
series |
OncoTargets and Therapy |
issn |
1178-6930 |
publishDate |
2019-04-01 |
description |
Xin-Hua Ruan,1,* Xi-Mei Liu,1,* Zhi-Xiang Yang,1,* Shao-Peng Zhang,1,* Quan-Zheng Li,1 Chun-Sheng Lin2 1Department of Cardiac Surgery, TianJin Union Medical Centre, Tianjin, People’s Republic of China; 2Department of Medical Service, TianJin Union Medical Centre, Tianjin, People’s Republic of China *These authors contributed equally to this work Background and objective: Inositol polyphosphate 4-phosphatase type II (INPP4B) is overexpressed in CRC tissues, and emerges as an oncogene. However, the mechanism by which INPP4B regulates CRC cell proliferation remains largely unclear. In this study, we aimed to investigate the regulatory mechanisms of INPP4B in CRC. Materials and methods: The expression levels of mRNA were detected by qRT-PCR. The expression levels of protein were determined by Western blot. Cell Counting Kit-8 (CCK-8) assays and BrdU incorporation assays were performed to evaluate cell proliferation abilities. Bicistronic luciferase assays and the m7GTP pull down assay were performed to measure the cap-dependent translation in cells. Results: INPP4B promotes CRC cell proliferation by increasing mTORC1 activity. Furthermore, it was shown that the activation of mTORC1 signaling by INPP4B led to increased cap-dependent translation, which is essential for INPP4B-mediated CRC cell proliferation. Finally, it was demonstrated that increased AKT and serum and glucocorticoid-inducible kinase 1 activity contributed to the activation of cap-dependent translation induced by INPP4B. Conclusion: Collectively, the present study reveals INPP4B promotes colorectal cancer cell proliferation by activating mTORC1 signaling and cap-dependent translation. Keywords: colorectal cancer, INPP4B, mTORC1, 4E-BP1, cap-dependent translation |
topic |
Colorectal cancer INPP4B mTORC1 4E-BP1 cap-dependent translation |
url |
https://www.dovepress.com/inpp4b-promotes-colorectal-cancer-cell-proliferation-by-activating-mto-peer-reviewed-article-OTT |
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