MicroRNA-365 inhibits proliferation, migration and invasion of glioma by targeting PIK3R3

Zhu,Yonggang; Zhao,Hongguang; Rao,Min; Xu,Songbai

doi:10.3892/or.2017.5458

MicroRNA-365 inhibits proliferation, migration and invasion of glioma by targeting PIK3R3

Authors:
- Yonggang Zhu
- Hongguang Zhao
- Min Rao
- Songbai Xu
View Affiliations

Affiliations: Department of Radiotherapy, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China, Department of Nuclear Medicine, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China, Department of Gastroenterology, The People's Republic Hospital of Jilin Province, Changchun, Jilin 130021, P.R. China, Department of Neurosurgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China
Published online on: February 16, 2017 https://doi.org/10.3892/or.2017.5458
Pages: 2185-2192

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

A growing body of evidence suggests that microRNA-365 (miR-365) played crucial role in the initiation and development of many types of cancers. However, the biological role of miR-365 in human glioma remains unclear. Herein, the aims of this study were to investigate the role and underlying mechanisms of miR-365 in glioma by a series of in vitro and in vivo experiments. We found that miR-365 was strongly downregulated in malignant glioma tissues and cell lines. Restoration of the expression of miR-365 in glioma cells significantly inhibited cell proliferation, migration and invasion in vitro and tumor growth in vivo. Notably, phosphoinositide-3-kinase regulatory subunit 3 (PIK3R3) was proved to be a direct target of miR-365 in glioma cells, and its mRNA expression was inversely correlated with miR-365 expression in clinical glioma tissues. PIK3R3 overexpression in miR-365 expressing cells could rescue proliferation, migration and invasion inhibition of miR-365. In addition, miR-365 was able to inhibit the phosphorylation of AKT and mTOR in vitro and in vivo, which are key participants in the AKT/mTOR pathway. These results suggest that miR-365 functioned as a tumor suppressor in glioma by targeting PIK3R3, suggesting that miR-365 has potential as therapeutic targets for glioma.

View Figures

View References

1	Reardon DA, Rich JN, Friedman HS and Bigner DD: Recent advances in the treatment of malignant astrocytoma. J Clin Oncol. 24:1253–1265. 2006. View Article : Google Scholar : PubMed/NCBI
2	Clarke J, Butowski N and Chang S: Recent advances in therapy for glioblastoma. Arch Neurol. 67:279–283. 2010. View Article : Google Scholar : PubMed/NCBI
3	Grauer OM, Wesseling P and Adema GJ: Immunotherapy of diffuse gliomas: Biological background, current status and future developments. Brain Pathol. 19:674–693. 2009. View Article : Google Scholar : PubMed/NCBI
4	Fabian MR, Sonenberg N and Filipowicz W: Regulation of mRNA translation and stability by microRNAs. Annu Rev Biochem. 79:351–379. 2010. View Article : Google Scholar : PubMed/NCBI
5	Guo H, Ingolia NT, Weissman JS and Bartel DP: Mammalian microRNAs predominantly act to decrease target mRNA levels. Nature. 466:835–840. 2010. View Article : Google Scholar : PubMed/NCBI
6	Almeida MI, Reis RM and Calin GA: MicroRNA history: Discovery, recent applications, and next frontiers. Mutat Res. 717:1–8. 2011. View Article : Google Scholar : PubMed/NCBI
7	Bartel DP: MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell. 116:281–297. 2004. View Article : Google Scholar : PubMed/NCBI
8	Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, Sweet-Cordero A, Ebert BL, Mak RH, Ferrando AA, et al: MicroRNA expression profiles classify human cancers. Nature. 435:834–838. 2005. View Article : Google Scholar : PubMed/NCBI
9	Farazi TA, Spitzer JI, Morozov P and Tuschl T: miRNAs in human cancer. J Pathol. 223:102–115. 2011. View Article : Google Scholar : PubMed/NCBI
10	McManus MT: MicroRNAs and cancer. Semin Cancer Biol. 13:253–258. 2003. View Article : Google Scholar : PubMed/NCBI
11	England B, Huang T and Karsy M: Current understanding of the role and targeting of tumor suppressor p53 in glioblastoma multiforme. Tumour Biol. 34:2063–2074. 2013. View Article : Google Scholar : PubMed/NCBI
12	Tivnan A and McDonald KL: Current progress for the use of miRNAs in glioblastoma treatment. Mol Neurobiol. 48:757–768. 2013. View Article : Google Scholar : PubMed/NCBI
13	Qi J, Rice SJ, Salzberg AC, Runkle EA, Liao J, Zander DS and Mu D: MiR-365 regulates lung cancer and developmental gene thyroid transcription factor 1. Cell Cycle. 11:177–186. 2012. View Article : Google Scholar : PubMed/NCBI
14	Sun R, Liu Z, Ma G, Lv W, Zhao X, Lei G and Xu C: Associations of deregulation of mir-365 and its target mRNA TTF-1 and survival in patients with NSCLC. Int J Clin Exp Pathol. 8:2392–2399. 2015.PubMed/NCBI
15	Bai J, Zhang Z, Li X and Liu H: MicroRNA-365 inhibits growth, invasion and metastasis of malignant melanoma by targeting NRP1 expression. Int J Clin Exp Pathol. 8:4913–4922. 2015.PubMed/NCBI
16	Guo SL, Ye H, Teng Y, Wang YL, Yang G, Li XB, Zhang C and Yang X, Yang ZZ and Yang X: Akt-p53-miR-365-cyclin D1/cdc25A axis contributes to gastric tumorigenesis induced by PTEN deficiency. Nat Commun. 4:25442013. View Article : Google Scholar : PubMed/NCBI
17	Gao J, Zhao P, Chen X, Wang W, Li Y, Xi W, Zhang W, Hu P, Wang T and Shan L: miR-365 inhibits proliferation and promotes apoptosis of SOSP9607 osteosarcoma cells. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 32:44–48. 2016.(In Chinese). PubMed/NCBI
18	Nie J, Liu L, Zheng W, Chen L, Wu X, Xu Y, Du X and Han W: microRNA-365, down-regulated in colon cancer, inhibits cell cycle progression and promotes apoptosis of colon cancer cells by probably targeting Cyclin D1 and Bcl-2. Carcinogenesis. 33:220–225. 2012. View Article : Google Scholar : PubMed/NCBI
19	Liu K, Li X, Cao Y, Ge Y, Wang J and Shi B: MiR-132 inhibits cell proliferation, invasion and migration of hepatocellular carcinoma by targeting PIK3R3. Int J Oncol. 47:1585–1593. 2015.PubMed/NCBI
20	Zhu Y, Zhao H, Feng L and Xu S: MicroRNA-217 inhibits cell proliferation and invasion by targeting Runx2 in human glioma. Am J Transl Res. 8:1482–1491. 2016.PubMed/NCBI
21	Cao G, Dong W, Meng X, Liu H, Liao H and Liu S: MiR-511 inhibits growth and metastasis of human hepatocellular carcinoma cells by targeting PIK3R3. Tumour Biol. 36:4453–4459. 2015. View Article : Google Scholar : PubMed/NCBI
22	Xu L, Wen Z, Zhou Y, Liu Z, Li Q, Fei G, Luo J and Ren T: MicroRNA-7-regulated TLR9 signaling-enhanced growth and metastatic potential of human lung cancer cells by altering the phosphoinositide-3-kinase, regulatory subunit 3/Akt pathway. Mol Biol Cell. 24:42–55. 2013. View Article : Google Scholar : PubMed/NCBI
23	Zhang L, Huang J, Yang N, Greshock J, Liang S, Hasegawa K, Giannakakis A, Poulos N, O'Brien-Jenkins A, Katsaros D, et al: Integrative genomic analysis of phosphatidylinositol 3′-kinase family identifies PIK3R3 as a potential therapeutic target in epithelial ovarian cancer. Clin Cancer Res. 13:5314–5321. 2007. View Article : Google Scholar : PubMed/NCBI
24	Chen Q, Guo W, Zhang Y, Wu Y and Xiang J: MiR-19a promotes cell proliferation and invasion by targeting RhoB in human glioma cells. Neurosci Lett. 628:161–166. 2016. View Article : Google Scholar : PubMed/NCBI
25	Peng T, Zhou L, Zuo L and Luan Y: MiR-506 functions as a tumor suppressor in glioma by targeting STAT3. Oncol Rep. 35:1057–1064. 2016.PubMed/NCBI
26	Zhou M, Liu W, Ma S, Cao H, Peng X, Guo L, Zhou X, Zheng L, Guo L, Wan M, et al: A novel onco-miR-365 induces cutaneous squamous cell carcinoma. Carcinogenesis. 34:1653–1659. 2013. View Article : Google Scholar : PubMed/NCBI
27	Hamada S, Masamune A, Miura S, Satoh K and Shimosegawa T: MiR-365 induces gemcitabine resistance in pancreatic cancer cells by targeting the adaptor protein SHC1 and pro-apoptotic regulator BAX. Cell Signal. 26:179–185. 2014. View Article : Google Scholar : PubMed/NCBI
28	Klahan S, Wu MS, Hsi E, Huang CC, Hou MF and Chang WC: Computational analysis of mRNA expression profiles identifies the ITG family and PIK3R3 as crucial genes for regulating triple negative breast cancer cell migration. BioMed Res Int. 2014:5365912014. View Article : Google Scholar : PubMed/NCBI
29	Xia X, Cheng A, Akinmade D and Hamburger AW: The N-terminal 24 amino acids of the p55 gamma regulatory subunit of phosphoinositide 3-kinase binds Rb and induces cell cycle arrest. Mol Cell Biol. 23:1717–1725. 2003. View Article : Google Scholar : PubMed/NCBI
30	Zhou J, Chen GB, Tang YC, Sinha RA, Wu Y, Yap CS, Wang G, Hu J, Xia X, Tan P, et al: Genetic and bioinformatic analyses of the expression and function of PI3K regulatory subunit PIK3R3 in an Asian patient gastric cancer library. BMC Med Genomics. 5:342012. View Article : Google Scholar : PubMed/NCBI
31	Wang G, Yang X, Li C, Cao X, Luo X and Hu J: PIK3R3 induces epithelial-to-mesenchymal transition and promotes metastasis in colorectal cancer. Mol Cancer Ther. 13:1837–1847. 2014. View Article : Google Scholar : PubMed/NCBI
32	Soroceanu L, Kharbanda S, Chen R, Soriano RH, Aldape K, Misra A, Zha J, Forrest WF, Nigro JM, Modrusan Z, et al: Identification of IGF2 signaling through phosphoinositide-3-kinase regulatory subunit 3 as a growth-promoting axis in glioblastoma. Proc Natl Acad Sci USA. 104:3466–3471. 2007. View Article : Google Scholar : PubMed/NCBI