摘要
背景与目的:研究表明垂体瘤转化基因1(pituitary tumor-transforming gene 1,PTTG1)在多种癌症中高表达。该研究旨在探讨其对胶质瘤细胞SHG44增殖、凋亡、迁移和侵袭能力的影响。方法:用PTTG1 siRNA干扰胶质瘤细胞SHG44的基因表达,通过实时荧光定量聚合酶链反应(real-time fluorescence quantitative polymerase chain reaction,RTFQ-PCR)和蛋白质印迹法(Western blot)分别在mRNA和蛋白质水平上评估PTTG1沉默效率,进一步检测其对SHG44细胞增殖、凋亡、迁移和侵袭能力的影响。结果:沉默PTTG1基因表达可以显著抑制SHG44细胞增殖(P<0.05)、迁移(P<0.01)和侵袭(P<0.001)能力,增加细胞凋亡(P<0.05)。结论:下调PTTG1的表达可以降低神经胶质瘤的恶化程度,有望成为临床胶质瘤治疗的新靶点。
Background and purpose: Some studies have showed that pituitary tumor-transforming gene 1(PTTG1) is highly expressed in many cancers. This study aimed to investigate the effects of PTTG1 on the proliferation, apoptosis, migration and invasion of glioma cells SHG44. Methods: PTTG1 siRNA was used to interfere with the gene expression of SHG44 in glioma cells. Real-time fluorescence quantitative polymerase chain reaction(RTFQ-PCR) and Western blot were used to evaluate the PTTG1 silencing efficiency at mRNA and protein levels. Furthermore, we tested the effects of PTTG1 on proliferation, apoptosis,migration and invasion of SHG44 cells. Results: The results showed that silencing PTTG1 gene expression significantly inhibited the proliferation(P<0.05), migration(P<0.01) and invasion(P<0.001) ability of SHG44 cells, and increased its apoptosis(P<0.05).Conclusion: Decreasing the expression of PTTG1 can inhibit the degree of glioma deterioration, and it is expected to become a new target for the treatment of glioma.
引文
[1]LIN L,CAI J,JIANG C.Recent advances in targeted therapy for glioma[J].Curr Med Chem,2017,24(13):1365-1381.
[2]PEI L,MELMED S.Isolation and characterization of a pituitary tumor-transforming gene(PTTG)[J].Mol Endocrinol,1997,11(4):433-441.
[3]WANG F,XUAN X Y,LI S L,et al.PTTG1 cooperated with Gli1leads to epithelial-mesenchymal transition in esophageal squamous cell cancer[J].Oncotarget,2017,8(54):92388-92400.
[4]NOLL J E,VANDYKE K,HEWETT D R,et al.PTTG1expression is associated with hyperproliferative disease and poor prognosis in multiple myeloma[J].J Hematol Oncol,2015,8(1):106.
[5]REN Q,JIN B.The clinical value and biological function of PTTG1 in colorectal cancer[J].Biomed Pharmacother,2017,89:108-115.
[6]ADDE R,RADHAKRISHNAN S,REDDIVARI L,et al.Triphala extract suppresses proliferation and induces apoptosis in human colon cancer stem cells via suppressing C-Myc/Cyclin D1 and elevation of Bax/Bcl-2 ratio[J].Biomed Res Int,2015,2015(1):649263.
[7]FIGARELLA-BRANGER D,COLIN C,COULIBALY B,et al.Histological and molecular classification of gliomas[J].Rev Neurol,2008,164(6):505-515.
[8]JUE T R,SENA E S,MACLEOD M R,et al.A systematic review and meta-analysis of topoisomerase inhibition in pre-clinical glioma models[J].Oncotarget,2018,9(13):11387-11401.
[9]YU R,HEANEY A,LU W,et al.Pituitary tumor transforming gene(PTTG)causes aneuploidy and p53-dependent and p53-inpendent apoptosis[J].J Biol Chem,2000,275(47):36502-36505.
[10]MOHEBALI J,WALSH M T,COULDWELL W T.Brainstem glioma in PHACES syndrome:case report and review of the literature[J].Cent Eur Neurosurg,2011,72(1):46-48.
[11]HAJI AMOUSHA M R,SABETKISH N,HESHMAT R,et al.Expression of the pituitary tumor transforming gene(PTTG1)in pheochromocytoma as a poteintial marker for distinguishing benign versus malignant tumors[J].Acta Med Iran,2015,53(4):236-241.
[12]CHEN L,PURI R,KAKAR S S,et al.Identification of the human pituitary tumor transforming gene(hPTTG)family:molecular structure,expression,and chromosomal localization[J].Gene,2000,248(1):41.
[13]ROY L O,POIRIER M B,FORTIN D.Transforming growth factor-beta and its implication in the malignancy of gliomas[J].Target Oncol,2015,10(1):1-14.
[14]CUI L,XU S,SONG Z,et al.Pituitary tumor transforming gene:a novel therapeutic target for glioma treatment[J].Acta Bioch Bioph Sin,2015,47(6):414-421.
[15]ZHANG E,LIU S,XU Z,et al.Pituitary tumor-transforming gene 1(PTTG1)is overexpressed in oral squamous cell carcinoma(OSCC)and promotes migration,invasion and epithelial-mesenchymal transition(EMT)in SCC15 cells[J].Tumour Biol,2014,35(9):8801-8811.