[an error occurred while processing this directive]|[an error occurred while processing this directive]
miR-361-5p负调控靶基因FoxM1增加骨肉瘤细胞放射敏感性研究
丁帅1 , 高延征1 , 张广泉1 , 陈书连1 , 曹臣1 , 李白羽2
1河南省人民医院脊柱脊髓外科,郑州 450003; 2河南省人民医院放疗科,郑州 450003
Mir-361-5p enhances radiosensitivity of osteosarcoma cells by directly downregulating FOXM1
Ding Shuai1, Gao Yanzheng1, Zhang Guangquan1, Chen Shulian1, Cao Chen1, Li Baiyu2
1Department of spine and spinal cord, Henan Province People′s Hospital,Zhengzhou,Henan,450003 China; 2Department of Cancer and Radiotherapy,Henan Province People′s Hospital,Zhengzhou,Henan,450003 China
Abstract:Objective To investigate the effect of microRNA361-5p on radiosensitivity of osteosarcoma cells and its downstream regulatory mechanisms.Methods The radioresistant osteosarcoma cell line HOS-R was constructed and the expression of microRNA-361-5p in HOS and HOS-R cells was detected by RT-qPCR.The survival rate and apoptosis rate were detected by clone formation assay and flow cytometry in HOS-R cells treated with up-regulated or down-regulated of miR-361-5p,or FOXM1 depletion. Dual fluorescent luciferase reporter and western blot assays were used to measure the relationship between miR-361-5p and FOXM1.he effects of miR-361-5p on radiosensitivity of osteosarcoma cells were determined by cloning formation assay and flow cytometry.Results RT-qPCRResults showed that miR-361-5p was low expressed in HOS-R cells. Colony formation and flow cytometry assays demonstrated that overexpression of miR-361-5p significantly decreased the survival rate and increased the apoptosis rate of HOS-R cells. In contrast,FOXM1 downregulation inhibited cell survival rate and induced apoptosis. Moreover,miR-361-5p negatively regulated FOXM1 expression. Besides,FOXM1 overexpression attenuated the miR-361-5p upregulation-mediated promotion of radiosensitivity in HOS-R cells.Conclusion miR-361-5p was involved in the radiosensitivity of osteosarcoma cells by inhibiting FOXM1.
Ding Shuai,Gao Yanzheng,Zhang Guangquan et al. Mir-361-5p enhances radiosensitivity of osteosarcoma cells by directly downregulating FOXM1[J]. Chinese Journal of Radiation Oncology, 2019, 28(5): 378-381.
[1]Mirabello L,Troisi RJ,Savage SA.Osteosarcoma incidence and survival rates from 1973 to 2004:data from the Surveillance,Epidemiology,and En.Results Program[J].Cancer,2010,115(7):1531-1543.DOI:10.1002/cncr.24121. [2]Shiomitsu K,Sajo E,Xia X,et al. Radiosensitivity of canine osteosarcoma cells transfected with wild-type p53 in vitro[J].Vet Comp Oncol,2010,6(3):193-200.DOI:10.1111/j.1476-5829.2008.00160.x. [3]刘威,顾康生.DNA损伤修复途径与微小RNA[J].安徽医科大学学报,2016,51(2):311-314.DOI:10.19405/j.cnki.issn1000-1492.2016.02.038 Liu W,Gu KS.DNA damage repair pathway and microRNA[J].Acta Universitatis Medicinalis Anhui,2016,51(2):311-314.DOI:10.19405/j.cnki.issn1000-1492.2016.02.038. [4]Popanda O,Ebbeler R,Twardella D,et al. Radiation-induced DNA damage and repair in lymphocytes from breast cancer patients and their correlation with acute skin reactions to radiotherapy[J].Int J Radiat Oncol Biol Phys,2003,55(5):1216-1225.DOI:10.1016/S0360-3016(02)04415-2. [5]朱霞,鲁康洋,江燕,等.FoxM1抑制剂下调Rad51增敏顺铂对骨肉瘤耐药细胞的化疗抑制作用[J].临床与实验病理学杂志,2017,33(4):403-407.DOI:10.13315/j.cnki.cjcep.2017.04.011. Zhu X,LU KY,Jiang Y,et al. FoxM1 inhibitor sensitize resistant osteosarcoma cells to cisplatin by down-regulation of Rad51[J].J Clin Exp Pathol,2017,33(4):403-407.DOI:10.13315/j.cnki.cjcep.2017.04.011. [6]刘林,康心琴,朱荣强.骨肉瘤中MZF1、FoxM1异常表达对细胞增殖、凋亡的影响[J].海南医学院学报,2018,24(4):440-443.DOI:10.13210/j.cnki.jhmu.20180205.001. Liu L,Kang XQ,Zhu RQ.Effect of abnormal MZF1 and FoxM1 expression on cell proliferation and apoptosis in osteosarcoma[J].J Hainan Med Univ.,2018,24(4):440-443.DOI:10.13210/j.cnki.jhmu.20180205.001. [7]荆玉龙,吕智.微RNA在骨肉瘤中的研究进展[J].肿瘤研究与临床,2016,28(9):638-641.DOI:10.3760/cma.j.issn.1006-9801.2016.09.017. Jing YL,Lv Z.Progress in microRNA in osteosarcoma[J].Cancer Res Clin,2016,28(9):638-641.DOI:10.3760/cma.j.issn.1006-9801.2016.09.017. [8]Tian L,Zhao Z,Xie L,et al. MiR-361-5p suppresses chemoresistance of gastric cancer cells by targeting FOXM1 via the PI3K/Akt/mTOR pathway[J].Oncotarget,2018,9(4):4886-4896.DOI:10.18632/oncotarget.23513. [9]Hou XW,Sun X,Yu Y,et al.miR-361-5p suppresses lung cancer cell lines progression by targeting FOXM1[J].Neoplasma,2017,64(4):526-534.DOI:10.4149/neo_2017_406. [10]党翠玲,孙影.FOXM1在恶性肿瘤中的研究[J].临床医药文献杂志,2018,5(26):181-182.DOI:10.16281/j.cnki.jocml.2018.26.103. Dang CL,Sun Y.Study of FOXM1 in Malignant Tumors[J].J Clin Med,2018,5(26):181-182.DOI:10.16281/j.cnki.jocml.2018.26.103. [11]李永峰.FoxM1在细胞周期和肿瘤中的研究进展[J].国际肿瘤学杂志,2011,V38(5):332-335.DOI:10.3760/cma.j.issn.1673-422X.2011.05.004. Li YF.FoxM1 research progress in cell cycle and tumor[J].J Int Oncol,2011,V38(5):332-335.DOI:10.3760/cma.j.issn.1673-422X.2011.05.004. [12]Koo CY,Muir KW,Lam EW.FOXM1:From cancer initiation to progression and treatment[J].Biochim Biophys Acta,2012,1819(1):28-37.DOI:10.1016/j.bbagrm.2011.09.004. [13]He S,Liao B,Deng Y,et al. MiR-216b inhibits cell proliferation by targeting FOXM1 in cervical cancer cells and is associated with better prognosis[J].Bmc Cancer,2017 Oct 4;17(1):673-684.DOI:10.1186/s12885-017-3650-5. [14]Inoguchi S,Seki N,Chiyomaru T,et al. Tumour-suppressive microRNA-24-1,inhibits cancer cell proliferation through targeting FOXM1,in bladder cancer[J].Febs Letters,2014,588(17):3170-3179.DOI:10.1016/j.febslet.2014.06.058.Epub 2014 Jul 3. [15]刘琅嬛,罗爱武,陈科良,等.FOXM1在食管鳞癌中的表达及对其放射敏感性的影响[J].辐射研究与辐射工艺学报,2016,34(6):21-28.DOI:10.11889/j.1000-3436.2016.rrj.34.060202. Liu LH,Luo AW,Chen KL,et al. Expression of FOXM1 and its effects on radiation sensitivity in esophageal squamous cell carcinoma (ESCC)[J].J Radiat Res Radiat Proc,2016,34(6):21-28.DOI:10.11889/j.1000-3436.2016.rrj.34.060202. [16]Li T,Ma J,Han X,et al. MicroRNA-320 Enhances Radiosensitivity of Glioma Through Down-Regulation of Sirtuin Type 1 by Directly Targeting Forkhead Box Protein M1[J].Transl Oncol,2018,11(2):205-212.DOI:10.1016/j.tranon.2017.12.008. [17]Xiu G,Sui X,Wang Y,et al. FOXM1 regulates radiosensitivity of lung cancer cell partly by upregulating KIF20A[J].Eur J Pharmacol,2018,833:79-85.DOI:10.1016/j.ejphar.2018.04.021.