Knockdown of JARID2 inhibits the proliferation and invasion of ovarian cancer through the PI3K/Akt signaling pathway

Cao,Jian; Li,Huiling; Liu,Guangquan; Han,Suping; Xu,Pengfei

doi:10.3892/mmr.2017.7024

Knockdown of JARID2 inhibits the proliferation and invasion of ovarian cancer through the PI3K/Akt signaling pathway

Authors:
- Jian Cao
- Huiling Li
- Guangquan Liu
- Suping Han
- Pengfei Xu
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Affiliations: Department of Obstetrics and Gynecology, Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University, Nanjing, Jiangsu 210004, P.R. China, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, P.R. China, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China, Nanjing Maternal and Child Health Institute, Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University, Nanjing, Jiangsu 210004, P.R. China
Published online on: July 17, 2017 https://doi.org/10.3892/mmr.2017.7024
Pages: 3600-3605

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Abstract

Protein Jumonji (JARID2), a member of the family of JmjC domain-containing proteins, has been reported to serve an important role in tumor growth and metastasis. However, the expression pattern and role of JARID2 in ovarian cancer remains unclear. Therefore, in the present study, the role of JARID2 in ovarian cancer was investigated, as well as the underlying mechanisms. The results of the present study demonstrated that the expression of JARID2 is upregulated in human ovarian cancer cell lines. Furthermore, downregulation of JARID2 significantly suppressed proliferation, migration, invasion and epithelial‑mesenchymal transition in human ovarian cancer cells. Mechanistically, downregulation of JARID2 decreased the protein expression levels of phosphorylated phosphoinositide 3‑kinase (PI3K) and protein kinase B (Akt) in ovarian cancer cells. In conclusion the observations suggested that knockdown of JARID2 inhibited proliferation, migration and invasion in vitro through the inactivation of the PI3K/Akt signaling pathway. Therefore, JARID2 may represent a potential therapeutic target for the treatment of ovarian cancer.

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1	Kuznia AL and Roett MA: Genital cancers in women: Ovarian cancer. FP Essent. 438:24–30. 2015.PubMed/NCBI
2	Nicoletto MO, Artioli G, Donach M, Sileni VC, Monfardini S, Talamini R, Veronesi A, Ferrazzi E, Tumolo S, Visonà E, et al: Elderly ovarian cancer: Treatment with mitoxantrone-carboplatin. Gynecol Oncol. 80:221–226. 2001. View Article : Google Scholar : PubMed/NCBI
3	Rustin GJ, van der Burg ME, Griffin CL, Guthrie D, Lamont A, Jayson GC, Kristensen G, Mediola C, Coens C, Qian W, et al: Early versus delayed treatment of relapsed ovarian cancer (MRC OV05/EORTC 55955): A randomised trial. Lancet. 376:1155–1163. 2010. View Article : Google Scholar : PubMed/NCBI
4	Harries M and Gore M: Part II: Chemotherapy for epithelial ovarian cancer-treatment of recurrent disease. Lancet Oncol. 3:537–545. 2002. View Article : Google Scholar : PubMed/NCBI
5	Sundar S, Neal RD and Kehoe S: Diagnosis of ovarian cancer. BMJ. 351:h44432015. View Article : Google Scholar : PubMed/NCBI
6	Qian Q, Yan Y, Yang J, Cao D, Zhu Z, Wu M, Chen J, Lang J and Shen K: Management and prognosis of patients with ovarian sex cord tumor with annular tubules: A retrospective study. BMC Cancer. 15:2702015. View Article : Google Scholar : PubMed/NCBI
7	Shirato H, Ogawa S, Nakajima K, Inagawa M, Kojima M, Tachibana M, Shinkai Y and Takeuchi T: A jumonji (Jarid2) protein complex represses cyclin D1 expression by methylation of histone H3-K9. J Biol Chem. 284:733–739. 2009. View Article : Google Scholar : PubMed/NCBI
8	Sanulli S, Justin N, Teissandier A, Ancelin K, Portoso M, Caron M, Michaud A, Lombard B, da Rocha ST, Offer J, et al: Jarid2 Methylation via the PRC2 complex regulates H3K27me3 deposition during cell differentiation. Mol Cell. 57:769–783. 2015. View Article : Google Scholar : PubMed/NCBI
9	Landeira D, Sauer S, Poot R, Dvorkina M, Mazzarella L, Jørgensen HF, Pereira CF, Leleu M, Piccolo FM, Spivakov M, et al: Jarid2 is a PRC2 component in embryonic stem cells required for multi-lineage differentiation and recruitment of PRC1 and RNA Polymerase II to developmental regulators. Nat Cell Biol. 12:618–624. 2010. View Article : Google Scholar : PubMed/NCBI
10	Peng JC, Valouev A, Swigut T, Zhang J, Zhao Y, Sidow A and Wysocka J: Jarid2/Jumonji coordinates control of PRC2 enzymatic activity and target gene occupancy in pluripotent cells. Cell. 139:1290–1302. 2009. View Article : Google Scholar : PubMed/NCBI
11	Walters ZS, Villarejo-Balcells B, Olmos D, Buist TW, Missiaglia E, Allen R, Al-lazikani B, Garrett MD, Blagg J and Shipley J: JARID2 is a direct target of the PAX3-FOXO1 fusion protein and inhibits myogenic differentiation of rhabdomyosarcoma cells. Oncogene. 33:1148–1157. 2014. View Article : Google Scholar : PubMed/NCBI
12	Tange S, Oktyabri D, Terashima M, Ishimura A and Suzuki T: JARID2 is involved in transforming growth factor-beta-induced epithelial-mesenchymal transition of lung and colon cancer cell lines. PLoS One. 9:e1156842014. View Article : Google Scholar : PubMed/NCBI
13	Zhu Z, Tang LS, Xu L, Qin X, Mao S, Song Y, Liu L, Li F, Liu P, Yi L, et al: Genome-wide association study identifies new susceptibility loci for adolescent idiopathic scoliosis in Chinese girls. Nat Commun. 6:83552015. View Article : Google Scholar : PubMed/NCBI
14	Lei X, Xu JF, Chang RM, Fang F, Zuo CH and Yang LY: JARID2 promotes invasion and metastasis of hepatocellular carcinoma by facilitating epithelial-mesenchymal transition through PTEN/AKT signaling. Oncotarget. 7:40266–40284. 2016. View Article : Google Scholar : PubMed/NCBI
15	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-tie quantitative PCR and the 2(−Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
16	Li L, Wang L, Zhang W, Tang B, Zhang J, Song H, Yao D, Tang Y, Chen X, Yang Z, et al: Correlation of serum VEGF levels with clinical stage, therapy efficacy, tumor metastasis and patient survival in ovarian cancer. Anticancer Res. 24:1973–1979. 2004.PubMed/NCBI
17	De Craene B and Berx G: Regulatory networks defining EMT during cancer initiation and progression. Nat Rev Cancer. 13:97–110. 2013. View Article : Google Scholar : PubMed/NCBI
18	Yilmaz M and Christofori G: EMT, the cytoskeleton, and cancer cell invasion. Cancer Metast Rev. 28:15–33. 2009. View Article : Google Scholar
19	Meng Q, Xia C, Fang J, Rojanasakul Y and Jiang BH: Role of PI3K and AKT specific isoforms in ovarian cancer cell migration, invasion and proliferation through the p70S6K1 pathway. Cell Signal. 18:2262–2271. 2006. View Article : Google Scholar : PubMed/NCBI
20	Huang J, Zhang L, Greshock J, Colligon TA, Wang Y, Ward R, Katsaros D, Lassus H, Butzow R, Godwin AK, et al: Frequent genetic abnormalities of the PI3K/AKT pathway in primary ovarian cancer predict patient outcome. Genes Chromosomes Cancer. 50:606–618. 2011. View Article : Google Scholar : PubMed/NCBI
21	Lau MT and Leung PC: The PI3K/Akt/mTOR signaling pathway mediates insulin-like growth factor 1-induced E-cadherin down-regulation and cell proliferation in ovarian cancer cells. Cancer Lett. 326:191–198. 2012. View Article : Google Scholar : PubMed/NCBI
22	Luo J, Manning BD and Cantley LC: Targeting the PI3K-Akt pathway in human cancer: Rationale and promise. Cancer Cell. 4:257–262. 2003. View Article : Google Scholar : PubMed/NCBI
23	Manning BD and Cantley LC: AKT/PKB signaling: Navigating downstream. Cell. 129:1261–1274. 2007. View Article : Google Scholar : PubMed/NCBI
24	Grille SJ, Bellacosa A, Upson J, Klein-Szanto AJ, van Roy F, Lee-Kwon W, Donowitz M, Tsichlis PN and Larue L: The protein kinase Akt induces epithelial mesenchymal transition and promotes enhanced motility and invasiveness of squamous cell carcinoma lines. Cancer Res. 63:2172–2178. 2003.PubMed/NCBI
25	Bai H, Li H, Li W, Gui T, Yang J, Cao D and Shen K: The PI3K/AKT/mTOR pathway is a potential predictor of distinct invasive and migratory capacities in human ovarian cancer cell lines. Oncotarget. 6:25520–25532. 2015. View Article : Google Scholar : PubMed/NCBI