CIP2A regulates proliferation and apoptosis of multiple myeloma cells

Zheng,Zhuanzhen; Qiao,Zhenhua; Chen,Wenliang; Gong,Rong; Wang,Yalin; Xu,Lianrong; Ma,Yanping; Zhang,Li; Lu,Yujin; Jiang,Bo; Li,Guoxia; Dong,Chunxia

doi:10.3892/mmr.2016.5553

CIP2A regulates proliferation and apoptosis of multiple myeloma cells

Authors:
- Zhuanzhen Zheng
- Zhenhua Qiao
- Wenliang Chen
- Rong Gong
- Yalin Wang
- Lianrong Xu
- Yanping Ma
- Li Zhang
- Yujin Lu
- Bo Jiang
- Guoxia Li
- Chunxia Dong
View Affiliations

Affiliations: Department of Hematology, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China, Shanxi Academy of Medical Sciences, Shanxi University Hospital, Taiyuan, Shanxi 030006, P.R. China, Department of Hematology, The Second People's Hospital of Shanxi, Taiyuan, Shanxi 037008, P.R. China
Published online on: July 27, 2016 https://doi.org/10.3892/mmr.2016.5553
Pages: 2705-2709

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Multiple myeloma (MM) is one of the most common causes of mortality from hematological malignancy in China. Recent studies have demonstrated that cancerous inhibitor of protein phosphatase 2A (CIP2A) may exhibit a role in promoting the growth of cancer; however, the function of CIP2A in MM remains unknown. In the present study, the expression and molecular mechanism underlying the effects of CIP2A in patients with MM and in MM cell lines were elucidated. Firstly, the expression of CIP2A was detected in patients with MM and in MM cell lines by reverse transcription‑quantitative polymerase chain reaction. Furthermore, silencing of CIP2A with short hairpin RNA was performed in MM cells, and the impact on the proliferation and apoptosis of RPMI‑8226 cells was analyzed (as endogenous CIP2A is highly expressed in RPMI‑8226 cell lines compared with other cells). CIP2A was significantly elevated in patients with MM and in MM cell lines, and silencing of CIP2A could inhibit the proliferation ability of RPMI‑8226 cells in vitro. In addition, CIP2A knockdown induced apoptosis and led to substantial reduction of c‑Myc protein levels in MM cell lines. This study suggested that CIP2A inhibition may provide a promising therapeutic strategy for patients with MM.

View Figures

View References

1	Hatzimichael E, Dasoula A, Benetatos L, Syed N, Dranitsaris G, Crook T and Bourantas K: Study of specific genetic and epigenetic variables in multiple myeloma. Leuk Lymphoma. 51:2270–2274. 2010. View Article : Google Scholar : PubMed/NCBI
2	Richards T and Weber D: Advances in treatment for relapses and refractory multiple myeloma. Med Oncol. 27(Suppl 1): S25–S42. 2010. View Article : Google Scholar : PubMed/NCBI
3	Laubach JP, Richardson PG and Anderson KC: The evolution and impact of therapy in multiple myeloma. Med Oncol. 27:S1–S6. 2010. View Article : Google Scholar : PubMed/NCBI
4	Khanna A, Böckelman C, Hemmes A, Junttila MR, Wiksten JP, Lundin M, Junnila S, Murphy DJ, Evan GI, Haglund C, et al: MYC-dependent regulation and prognostic role of CIP2A in gastric cancer. J Natl Cancer Inst. 101:793–805. 2009. View Article : Google Scholar : PubMed/NCBI
5	Johnson MD, Reeder JE, O'Connell M, Woodford M and Walter K: CIP2A and PP2A in human leptomeninges, arachnoid granulations and meningiomas. J Clin Neurosci. 21:2228–2232. 2014. View Article : Google Scholar : PubMed/NCBI
6	Li W, Ge Z, Liu C, Liu Z, Björkholm M, Jia J and Xu D: CIP2A is overexpressed in gastric cancer and its depletion leads to impaired clonogenicity, senescence, or differentiation of tumor cells. Clin Cancer Res. 14:3722–3728. 2008. View Article : Google Scholar : PubMed/NCBI
7	Junttila MR, Puustinen P, Niemelä M, Ahola R, Arnold H, Böttzauw T, Ala-aho R, Nielsen C, Ivaska J, Taya Y, et al: CIP2A inhibits PP2A in human malignancies. Cell. 130:51–62. 2007. View Article : Google Scholar : PubMed/NCBI
8	Choi YA, Park JS, Park MY, Oh KS, Lee MS, Lim JS, Kim KI, Kim KY, Kwon J, Yoon do Y, et al: Increase in CIP2A expression is associated with doxorubicin resistance. FEBS Lett. 585:755–760. 2011. View Article : Google Scholar : PubMed/NCBI
9	Terpos E, Morgan G, Dimopoulos MA, Drake MT, Lentzsch S, Raje N, Sezer O, García-Sanz R, Shimizu K, Turesson I, et al: International myeloma working group recommendations for the treatment of multiple myeloma-related bone disease. J Clin Oncol. 31:2347–2357. 2013. View Article : Google Scholar : PubMed/NCBI
10	Nasri M, Karimi A and Allahbakhshian Farsani M: Production, purification and titration of a lentivirus-based vector for gene delivery purposes. Cytotechnology. 66:1031–1038. 2014. View Article : Google Scholar : PubMed/NCBI
11	Zhan F, Huang Y, Colla S, Stewart JP, Hanamura I, Gupta S, Epstein J, Yaccoby S, Sawyer J, Burington B, et al: The molecular classification of multiple myeloma. Blood. 108:2020–2028. 2006. View Article : Google Scholar : PubMed/NCBI
12	Pang X, Fu X, Chen S, Zhu X, Qi H, Li Y, Li F and Tan W: Overexpression of CIP2A promotes bladder cancer progression by regulating EMT. Clin Transl Oncol. 18:289–295. 2016. View Article : Google Scholar
13	Khanna A, Rane JK, Kivinummi KK, Urbanucci A, Helenius MA, Tolonen TT, Saramäki OR, Latonen L, Manni V, Pimanda JE, et al: CIP2A is a candidate therapeutic target in clinically challenging prostate cancer cell populations. Oncotarget. 6:19661–19670. 2015. View Article : Google Scholar : PubMed/NCBI
14	Ventelä S, Sittig E, Mannermaa L, Mäkelä JA, Kulmala J, Löyttyniemi E, Strauss L, Cárpen O, Toppari J, Grénman R and Westermarck J: CIP2A is an Oct4 target gene involved in head and neck squamous cell cancer oncogenicity and radioresistance. Oncotarget. 6:144–158. 2015.
15	Junttila MR, Puustinen P, Niemelä M, Ahola R, Arnold H, Böttzauw T, Ala-aho R, Nielsen C, Ivaska J, Taya Y, et al: CIP2A inhibits PP2A in human malignancies. Cell. 130:51–62. 2007. View Article : Google Scholar : PubMed/NCBI
16	De P, Carlson J, Leyland-Jones B and Dey N: Oncogenic nexus of cancerous inhibitor of protein phosphatase 2A (CIP2A): An oncoprotein with many hands. Oncotarget. 5:4581–4602. 2014. View Article : Google Scholar : PubMed/NCBI
17	Böckelman C, Lassus H, Hemmes A, Leminen A, Westermarck J, Haglund C, Bützow R and Ristimäki A: Prognostic role of CIP2A expression in serous ovarian cancer. Br J Cancer. 105:989–995. 2011. View Article : Google Scholar :
18	Yeh E, Cunningham M, Arnold H, Chasse D, Monteith T, Ivaldi G, Hahn WC, Stukenberg PT, Shenolikar S, Uchida T, et al: A signaling pathway controlling c-Myc degradation that impacts oncogenic transformation of human cells. Nat Cell Biol. 6:308–318. 2004. View Article : Google Scholar : PubMed/NCBI