Inhibitory role of human pituitary tumor-transforming gene 1 on apoptosis of ovary cancer cell line A2780 and its molecular mechanism_West China Medical Journal

Authors：

CHEN Jingyang ¹ , WANG Yilin ² , WANG Lin ² ,  LIU Jie ³

1. Department of Biochemistry and Molecular Biology, College of Basic Medical Science, China Medical University, Shenyang, Liaoning 110122, P. R. China;
2. The Second Clinical College of China Medical University, Shenyang, Liaoning 110013, P. R. China;
3. The Science Experiment Center of China Medical University, Shenyang, Liaoning 110122, P. R. China;

Corresponding author：

LIU Jie, Email: lj6152003@163.com

Keywords：

Human pituitary tumor-transforming gene 1; Ovarian cancer; Small interference RNA; Survivin; Caspase-3

DOI：

10.7507/1002-0179.201704187

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Objective To investigate the effects and underlying mechanisms of human pituitary tumor-transforming gene 1 (hPTTG1) small interfering RNA (siRNA) on apoptosis of ovarian cancer cell line A2780. Methods hPTTG1 siRNA was transfected into A2780 with lipofectamine (the hPTTG1 siRNA group), and the normal group and the negative control group were set up. Detections were conducted 48 hours after transfection: the interfering efficiency of hPTTG1 mRNA was measured by real-time polymerase chain reaction, the expression of survivin gene and survivin protein was examined by semiquantitative reverse transcriptase-polymerase chain reaction and Western blot, cell apoptosis was detected by DNA fragmentation gel electrophoresis and propidium iodide staining kit, and the activity of caspase-3 was assayed by caspases colorimetric assay kit. Results The expression of hPTTG1 mRNA was expressly inhibited after hPTTG1 siRNA transfection. DNA ladder was observed in the hPTTG1 siRNA group. The apoptotic rate of hPTTG1 siRNA transfection in the hPTTG1 siRNA group was (17.53±2.17)%, higher than those in the normal group and the negative control group [(8.97±1.56)% and (9.64±1.31)%, respectively], with statistically significant differences between them (P<0.05). The expression levels of survivin mRNA and survivin protein were down-regulated. The activity of caspase-3 was raised. Conclusions siRNA targeting hPTTG1 could induce apoptosis of A2780 by inhibition of survivin expression and activation of caspase-3. It may be a potential target for gene therapy of ovarian cancer.

Citation： CHEN Jingyang, WANG Yilin, WANG Lin, LIU Jie. Inhibitory role of human pituitary tumor-transforming gene 1 on apoptosis of ovary cancer cell line A2780 and its molecular mechanism. West China Medical Journal, 2017, 32(11): 1734-1738. doi: 10.7507/1002-0179.201704187 Copy

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8.	Kanter M, Turan G, Usta C, et al. Survivin and cycline D1 expressions are associated with malignant potential in mucinous ovarian neoplasms. J Mol Histol, 2016, 47(2): 145-152.
9.	Ren Q, Jin B. The clinical value and biological function of PTTG1 in colorectal cancer. Biomed Pharmacother, 2017, 89: 108-115.
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11.	Xie YS, Wang R. Pttg1 promotes growth of breast cancer through P27 nuclear exclusion. Cell Physiol Biochem, 2016, 38(1): 393-400.
12.	Xu MD, Dong L, Qi P, et al. Pituitary tumor-transforming gene-1 serves as an independent prognostic biomarker for gastric cancer. Gastric Cancer, 2016, 19(1): 107-115.
13.	Fan Y, Chen J. Clinicopathological significance of survivin expression in patients with cervical cancer: a systematic meta-analysis. Bioengineered, 2017, 4: 1-13.
14.	Plewka D, Jakubiec-Bartnik B, Morek M, et al. Survivin in ovary tumors. Ginekol Pol, 2015, 86(7): 525-530.
15.	Mak CS, Yung MM, Hui LM, et al. MicroRNA-141 enhances anoikis resistance in metastatic progression of ovarian cancer through targeting KLF12/Sp1/survivin axis. Mol Cancer, 2017, 16(1): 11.
16.	Sapiezynski J, Taratula O, Rodriguez-Rodriguez L, et al. Precision targeted therapy of ovarian cancer. J Control Release, 2016, 243: 250-268.
17.	Ozcan G, Ozpolat B, Coleman RL, et al. Preclinical and clinical development of siRNA-based therapeutics. Adv Drug Deliv Rev, 2015, 87: 108-119.

1. Ziebarth AJ, Landen CN Jr, Alvarez RD, et al. Molecular/genetic therapies in ovarian cancer: future opportunities and challenges. Clin Obstet Gynecol, 2012, 55(1): 156-172.
2. Wang X, Duan W, Li X, et al. PTTG regulates the metabolic switch of ovarian cancer cells via the c-myc pathway. Oncotarget, 2015, 6(38): 40959-40969.
3. Nakachi I, Helfrich BA, Spillman MA, et al. PTTG1 levels are predictive of saracatinib sensitivity in ovarian cancer cell lines. Clin Transl Sci, 2016, 9(6): 293-301.
4. Panguluri SK, Yeakel C, Kakar SS. PTTG: an important target gene for ovarian cancer therapy. J Ovarian Res, 2008, 1(1): 6.
5. El-Naggar SM, Malik MT, Kakar SS. Small interfering RNA against PTTG: a novel therapy for ovarian cancer. Int J Oncol, 2007, 31(1): 137-143.
6. Shamsabadi FT, Eidgahi MR, Mehrbod P, et al. Survivin, a promising gene for targeted cancer treatment. Asian Pac J Cancer Prev, 2016, 17(8): 3711-3719.
7. Garg H, Suri P, Gupta JC, et al. Survivin: a unique target for tumor therapy. Cancer Cell Int, 2016, 23(16): 49.
8. Kanter M, Turan G, Usta C, et al. Survivin and cycline D1 expressions are associated with malignant potential in mucinous ovarian neoplasms. J Mol Histol, 2016, 47(2): 145-152.
9. Ren Q, Jin B. The clinical value and biological function of PTTG1 in colorectal cancer. Biomed Pharmacother, 2017, 89: 108-115.
10. Su X, Chen J, Ni L, et al. Inhibition of PTTG1 expression by microRNA suppresses proliferation and induces apoptosis of malignant glioma cells. Oncol Lett, 2016, 12(5): 3463-3471.
11. Xie YS, Wang R. Pttg1 promotes growth of breast cancer through P27 nuclear exclusion. Cell Physiol Biochem, 2016, 38(1): 393-400.
12. Xu MD, Dong L, Qi P, et al. Pituitary tumor-transforming gene-1 serves as an independent prognostic biomarker for gastric cancer. Gastric Cancer, 2016, 19(1): 107-115.
13. Fan Y, Chen J. Clinicopathological significance of survivin expression in patients with cervical cancer: a systematic meta-analysis. Bioengineered, 2017, 4: 1-13.
14. Plewka D, Jakubiec-Bartnik B, Morek M, et al. Survivin in ovary tumors. Ginekol Pol, 2015, 86(7): 525-530.
15. Mak CS, Yung MM, Hui LM, et al. MicroRNA-141 enhances anoikis resistance in metastatic progression of ovarian cancer through targeting KLF12/Sp1/survivin axis. Mol Cancer, 2017, 16(1): 11.
16. Sapiezynski J, Taratula O, Rodriguez-Rodriguez L, et al. Precision targeted therapy of ovarian cancer. J Control Release, 2016, 243: 250-268.
17. Ozcan G, Ozpolat B, Coleman RL, et al. Preclinical and clinical development of siRNA-based therapeutics. Adv Drug Deliv Rev, 2015, 87: 108-119.

West China Medical Journal

Inhibitory role of human pituitary tumor-transforming gene 1 on apoptosis of ovary cancer cell line A2780 and its molecular mechanism

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