Pim1 promotes cell proliferation and regulates glycolysis via interaction with MYC in ovarian cancer

Yong Wu,1,2 Yu Deng,2,3 Jun Zhu,1,2 Yachen Duan,1,2 WeiWei Weng,2,3 Xiaohua Wu1,2 1Department of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Shanghai, People’s Republic of China; 2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People&r...

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Main Authors: Wu Y, Deng Y, Zhu J, Duan Y, Weng W, Wu XH
Format: Article
Language:English
Published: Dove Medical Press 2018-10-01
Series:OncoTargets and Therapy
Subjects:
Online Access:https://www.dovepress.com/pim1-promotes-cell-proliferation-and-regulates-glycolysis-via-interact-peer-reviewed-article-OTT
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spelling doaj-c5dffcda4be2426d85a6e90158abc97c2020-11-24T21:27:09ZengDove Medical PressOncoTargets and Therapy1178-69302018-10-01Volume 116647665641238Pim1 promotes cell proliferation and regulates glycolysis via interaction with MYC in ovarian cancerWu YDeng YZhu JDuan YWeng WWu XHYong Wu,1,2 Yu Deng,2,3 Jun Zhu,1,2 Yachen Duan,1,2 WeiWei Weng,2,3 Xiaohua Wu1,2 1Department of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Shanghai, People’s Republic of China; 2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China; 3Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, People’s Republic of China Background: Ovarian cancer (OC) is the leading cause of death among women with gynecologic malignancies. Recent studies have highlighted the role of Pim1, which belongs to a group of constitutively activated serine/threonine kinases, in cancer development. However, the effect of Pim1 in OC is largely unclear. Methods: OC cell lines with Pim1 overexpression or knockdown were constructed with lentivirus transduction. Cell Counting Kit-8, colony formation, glycolysis stress test and in vivo mice models were carried out to assess the effect of Pim1 on OC biological functions. Co-immunoprecipitation assay coupled with western blot were performed to explore the intrinsic mechanisms of Pim1 in OC. Bioinformatic analysis was then performed to evaluate the expression and prognostic value of Pim1. Results: We present the first evidence that silencing or overexpressing Pim1 can suppress or promote, respectively, OC cell proliferation. Furthermore, we demonstrated that Pim1 can significantly enhance glycolysis in OC cells. In vivo experiments further confirmed that knockdown of Pim1 inhibits the growth of tumors derived from the SKOV3 cell line. To search for the underlying molecular mechanism, we examined the effect of Pim1 on MYC, a pivotal gene in glycolysis, and observed that Pim1-mediated phosphorylation of c-Myc activated the expression of glycolysis-associated key genes such as PGK1 and LDHA. Moreover, we found that the Pim1 inhibitor SMI4a induced chemosensitization to cisplatin. Clinically, Pim1 was also overexpressed in OC and correlated with poor overall survival by bioinformatics analysis. Conclusion: Together, these results suggest that Pim1 contributes to proliferation and glycolysis in OC via interaction with MYC and may serve as a potential target in the treatment of OC patients. Keywords: Pim1, ovarian cancer, c-Myc, glycolysis, SMI4a, therapeutic targethttps://www.dovepress.com/pim1-promotes-cell-proliferation-and-regulates-glycolysis-via-interact-peer-reviewed-article-OTTPim1ovarian cancerc-Mycglycolysis
collection DOAJ
language English
format Article
sources DOAJ
author Wu Y
Deng Y
Zhu J
Duan Y
Weng W
Wu XH
spellingShingle Wu Y
Deng Y
Zhu J
Duan Y
Weng W
Wu XH
Pim1 promotes cell proliferation and regulates glycolysis via interaction with MYC in ovarian cancer
OncoTargets and Therapy
Pim1
ovarian cancer
c-Myc
glycolysis
author_facet Wu Y
Deng Y
Zhu J
Duan Y
Weng W
Wu XH
author_sort Wu Y
title Pim1 promotes cell proliferation and regulates glycolysis via interaction with MYC in ovarian cancer
title_short Pim1 promotes cell proliferation and regulates glycolysis via interaction with MYC in ovarian cancer
title_full Pim1 promotes cell proliferation and regulates glycolysis via interaction with MYC in ovarian cancer
title_fullStr Pim1 promotes cell proliferation and regulates glycolysis via interaction with MYC in ovarian cancer
title_full_unstemmed Pim1 promotes cell proliferation and regulates glycolysis via interaction with MYC in ovarian cancer
title_sort pim1 promotes cell proliferation and regulates glycolysis via interaction with myc in ovarian cancer
publisher Dove Medical Press
series OncoTargets and Therapy
issn 1178-6930
publishDate 2018-10-01
description Yong Wu,1,2 Yu Deng,2,3 Jun Zhu,1,2 Yachen Duan,1,2 WeiWei Weng,2,3 Xiaohua Wu1,2 1Department of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Shanghai, People’s Republic of China; 2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China; 3Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, People’s Republic of China Background: Ovarian cancer (OC) is the leading cause of death among women with gynecologic malignancies. Recent studies have highlighted the role of Pim1, which belongs to a group of constitutively activated serine/threonine kinases, in cancer development. However, the effect of Pim1 in OC is largely unclear. Methods: OC cell lines with Pim1 overexpression or knockdown were constructed with lentivirus transduction. Cell Counting Kit-8, colony formation, glycolysis stress test and in vivo mice models were carried out to assess the effect of Pim1 on OC biological functions. Co-immunoprecipitation assay coupled with western blot were performed to explore the intrinsic mechanisms of Pim1 in OC. Bioinformatic analysis was then performed to evaluate the expression and prognostic value of Pim1. Results: We present the first evidence that silencing or overexpressing Pim1 can suppress or promote, respectively, OC cell proliferation. Furthermore, we demonstrated that Pim1 can significantly enhance glycolysis in OC cells. In vivo experiments further confirmed that knockdown of Pim1 inhibits the growth of tumors derived from the SKOV3 cell line. To search for the underlying molecular mechanism, we examined the effect of Pim1 on MYC, a pivotal gene in glycolysis, and observed that Pim1-mediated phosphorylation of c-Myc activated the expression of glycolysis-associated key genes such as PGK1 and LDHA. Moreover, we found that the Pim1 inhibitor SMI4a induced chemosensitization to cisplatin. Clinically, Pim1 was also overexpressed in OC and correlated with poor overall survival by bioinformatics analysis. Conclusion: Together, these results suggest that Pim1 contributes to proliferation and glycolysis in OC via interaction with MYC and may serve as a potential target in the treatment of OC patients. Keywords: Pim1, ovarian cancer, c-Myc, glycolysis, SMI4a, therapeutic target
topic Pim1
ovarian cancer
c-Myc
glycolysis
url https://www.dovepress.com/pim1-promotes-cell-proliferation-and-regulates-glycolysis-via-interact-peer-reviewed-article-OTT
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