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...

Full description

Bibliographic Details
Main Authors: Ruan X, Liu X, Yang Z, Zhang S, Li Q, Lin C
Format: Article
Language:English
Published: Dove Medical Press 2019-04-01
Series:OncoTargets and Therapy
Subjects:
Online Access:https://www.dovepress.com/inpp4b-promotes-colorectal-cancer-cell-proliferation-by-activating-mto-peer-reviewed-article-OTT
id doaj-0905acfb563a484d96c776365b2bdf0a
record_format Article
spelling 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
work_keys_str_mv AT ruanx inpp4bpromotescolorectalcancercellproliferationbyactivatingmtorc1signalingandcapdependenttranslation
AT liux inpp4bpromotescolorectalcancercellproliferationbyactivatingmtorc1signalingandcapdependenttranslation
AT yangz inpp4bpromotescolorectalcancercellproliferationbyactivatingmtorc1signalingandcapdependenttranslation
AT zhangs inpp4bpromotescolorectalcancercellproliferationbyactivatingmtorc1signalingandcapdependenttranslation
AT liq inpp4bpromotescolorectalcancercellproliferationbyactivatingmtorc1signalingandcapdependenttranslation
AT linc inpp4bpromotescolorectalcancercellproliferationbyactivatingmtorc1signalingandcapdependenttranslation
_version_ 1716806331479883776