Pim1 promotes cell proliferation and regulates glycolysis via interaction with MYC in ovarian cancer
Received 18 July 2018
Accepted for publication 15 August 2018
Published 9 October 2018 Volume 2018:11 Pages 6647—6656
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Andrew Yee
Peer reviewer comments 3
Editor who approved publication: Dr William Cho
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
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