Original Article
 

Mir-22-3p Enhances the Chemosensitivity of Gastrointestinal Stromal Tumor Cell Lines to Cisplatin through PTEN/PI3K/Akt Pathway

Abstract

Mir-22-3p is associated with many important biological processes, including neuroprotection, tumorigenesis, and various other tumor progressions. Our study aimed to investigate the roles of Mir-22-3p in chemosensitivity of gastrointestinal stromal tumor (GIST-T1) cells to cisplatin and explore its underlying mechanisms. Mir-22-3p high-expressing cell line was established by transfecting GIST-T1 cell line cells with Mir-22-3p mimic. After treatment with cisplatin (10 μM), Cell counting kits-8 (CCK-8) method was used to detect the cell viability. Flow cytometry was applied to measure the degree of cell apoptosis. Scratch wound healing test was used to detect the migration ability of cells. The protein and mRNA levels of the phosphatase and tensin homolog deleted on chromosome ten (PTEN)/phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt) pathway-related factors were analyzed by Western blot and qRT-PCR. The mRNA level of Mir-22-3p was increased in transfected GIST-T1 cells compared with that in control cells. The survival rate and Bcl-2/Bax ratio of GIST-T1 cells treated with both Mir-22-3p analogue and cisplatin were significantly decreased, while the apoptosis rate and protein level of caspase-3 were significantly increased (p<0.05). In addition, the mRNA and protein levels of PTENwere significantly increased in cells treated with both Mir-22-3p analogue and cisplatin (p<0.05), while the expression levels of PI3K and Akt were significantly decreased (p<0.05). Mir-22-3p overexpression can increase the chemosensitivity of cisplatin in human gastrointestinal stromal tumor cells by PTEN/PI3K/Akt pathway.  

  1. Utz P J, Anderson P. Life and death decisions: regulation of apoptosis by proteolysis of signaling molecules. Cell Death & Differentiation 2000, 7(7):589.
  2. Rejniak KA, Anderson AR. Hybrid models of tumor growth. Wiley Interdiscip Rev Syst Biol Med 2011; 3(1):115-25.
  3. De Luca A1, Maiello MR, D'Alessio A, Pergameno M, Normanno N. The RAS/RAF/MEK/ERK and the PI3K/AKT signalling pathways: role in cancer pathogenesis and implications for therapeutic approaches. Expert Opin Ther Targets 2012; 16(Suppl 2):S17-7.
  4. Carnero A, Blanco-Aparicio C, Renner O, Link W, Leal JF. The PTEN/PI3K/AKT signalling pathway in cancer, therapeutic implications. Curr Cancer Drug Targets 2008; 8(3):187-98.
  5. Porta C, Paglino C, Mosca A. Targeting PI3K/Akt/mTOR signaling in cancer. Front Oncol 2014; 4:64.
  6. Engelman JA, Luo J, Cantley LC. The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism. Nat Rev Genet 2006; 7(8):606-19.
  7. Franke TF. PI3K/Akt: getting it right matters. Oncogene 2008; 27(50):6473-88.
  8. Bar N, Dikstein R. miR-22 Forms a Regulatory Loop in PTEN/AKT Pathway and Modulates Signaling Kinetics. PLoS ONE 2010; 5(5):e10859.
  9. Xue G, Restuccia DF, Lan Q, Hynx D, Dirnhofer S, Hess D, et al. Akt/PKB-mediated phosphorylation of Twist1 promotes tumor metastasis via mediating cross-talk between PI3K/Akt and TGF-β signaling axes. Cancer Discov 2012; 2(3):248-59.
  10. Alessi DR, Andjelkovic M, Caudwell B, Cron P, Morrice N, Cohen P, et al. Mechanism of activation of protein kinase B by insulin and IGF-1. EMBO J 1996; 15(23):6541-51.
  11. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell 2011; 144(5):646-74.
  12. Zhao G, Cai C, Yang T, Qiu X, Liao B, Li W, et al. MicroRNA-221 Induces Cell Survival and Cisplatin Resistance through PI3K/Akt Pathway in Human Osteosarcoma. PLoS ONE 2013; 8(1):e53906.
  13. Schee K, Lorenz S, Worren MM, Günther CC, Holden M, Hovig E, et al. Deep Sequencing the MicroRNA Transcriptome in Colorectal Cancer. PLoS One 2013; 8:e66165.
  14. Qi B, Ji Q, Wen YC, Liu L, Guo XL, Hou GH, et al. Lycium barbarum polysacccharides Protect Human Lens Epithelial Cells against oxidative stress-induced apoptosis and senescence. PLOS One 2014; 9:e110275.
  15. Hafsi S, Pezzino FM, Candido S, Ligresti G, Spandidos DA, Soua Z, et al. Gene alterations in the PI3K/PTEN/AKT pathway as a mechanism of drug-resistance (review). Int J Oncol 2012; 40(3):639-44.
  16. Vivanco I, Sawyers CL. The phosphatidylinositol 3-Kinase AKT pathway in human cancer. Nat Rev Cancer 2002; 2:489-501.
  17. Di Cristofano A, Kotsi P, Peng YF, Cordon-Cardo C, Elkon KB, Pandolfi PP. Impaired fas response and autoimmunity in Pten+/− mice. Science 1999; 285(5436):2122-5.
  18. Ahmad A, Biersack B, Li Y, Kong D, Bao B, Schobert R, et al. Targeted regulation of PI3K/Akt/mTOR/NF-κB signaling by indole compounds and their derivatives: mechanistic details and biological implications for cancer therapy. Anticancer Agents Med Chem 2013; 13(7):1002-13.
  19. Hemmings BA, Restuccia DF. Pi3k-pkb/akt pathway. Cold Spring Harb Perspect Biol 2015; 7:a026609.
  20. Wang X, Liu JZ, Hu JX, Wu H, Li YL, Chen HL, et al. ROS-activated p38 MAPK/ERK-Akt cascade plays a central role in palmitic acid-stimulated hepatocyte proliferation. Free Radic Biol Med 2011; 51(2):539-51.
  21. Saini KS, Loi S, de Azambuja E, Metzger-Filho O, Saini ML, Ignatiadis M, Dancey JE, et al. Targeting the PI3K/AKT/mTOR and Raf/MEK/ERK pathways in the treatment of breast cancer. Cancer Treat Rev 2013; 39(8):935-46.
  22. Song MS, Salmena L, Pandolfi PP. The functions and regulation of the PTEN tumour suppressor. Nat Rev Mol Cell Biol 2012; 13(5):283-96.
  23. Davies EM, Sheffield DA, Tibarewal P, Fedele CG, Mitchell CA, Leslie NR. The PTEN and myotubularin phosphoinositide 3-phosphatases: linking lipid signalling to human disease. Subcell Biochem 2012; 58:281-336.
  24. Osaki M, Oshimura M, Ito H. PI3K-Akt pathway: its functions and alterations in human cancer. Apoptosis 2004; 9(6):667-76.

Files
IssueVol 17, No 4 (2018) QRcode
SectionOriginal Article(s)
DOI https://doi.org/10.18502/ijaai.v17i4.91
PMID30537795
Keywords
Chemosensitivity Cisplatin Gastrointestinal stromal tumor Mir-22-3p

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How to Cite
1.
Xu Y, Cheng M, Mi L, Qiu Y, Hao W, Li L. Mir-22-3p Enhances the Chemosensitivity of Gastrointestinal Stromal Tumor Cell Lines to Cisplatin through PTEN/PI3K/Akt Pathway. Iran J Allergy Asthma Immunol. 2018;17(4):318-325.