|Table of Contents|

The study of miR-34s enhancing the radiosensitivity of colorectal cancer cells

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2023 14
Page:
2588-2592
Research Field:
Publishing date:

Info

Title:
The study of miR-34s enhancing the radiosensitivity of colorectal cancer cells
Author(s):
CHEN Shuangjing1GAO Qichen1ZENG Hao1WANG Jun2ZHU Zheng1LIU Bo1SU Pu1
1.Research Department;2.Pharmacy Department,PLA Rocket Force Characteristic Medical Center,Beijing 100088,China.
Keywords:
colorectal cancerradiosensitivitymiR-34sDNA double strand breaks
PACS:
R735.3
DOI:
10.3969/j.issn.1672-4992.2023.14.005
Abstract:
Objective:To investigate the effects of miR-34s on the radiosensitivity of colorectal cancer (CRC) cells and the role of miR-34s in ionizing radiation-induced DNA damage.Methods:Real-time quantitative fluorescence PCR (qRT-PCR) was used to detect the expression of miR-34a/b/c-5p in CRC cells and the expression trend within 24 h after ionizing radiation.Cell survival curves were established based on clonogenic assay and multitarget/single-hit model to analyze the effects of miR-34a/b/c-5p on the radiosensitivity of CRC cells.Cells overexpressing miR-34a/b/c-5p were exposed to ionizing radiation,and γH2AX foci were detected using immunofluorescence assay after irradiation to analyze the effects of miR-34a/b/c-5p on ionizing radiation-induced DNA damage.Results:The expression levels of miR-34a/b/c-5p in HCT116 cells were significantly higher than that in HT29 cells (P<0.05).Within 24 h after 4 Gy irradiation,miR-34a/b/c-5p showed a bimodal expression pattern in HCT116 cells.Compared with the miR-NC group,overexpression of miR-34a/b/c-5p could significantly enhance the radiosensitivity of CRC cells.The mean lethal dose (D0) and quasi-threshold dose (Dq) were significantly decreased in the miR-34a/b/c-5p group,while the sensitizing enhancement ratio (SER) was significantly increased.Overexpression of miR-34a/b/c-5p significantly increased the level of ionizing radiation-induced DNA double strand breaks (DSBs),and the number of γH2AX foci in miR-34a/b/c-5p group were significantly higher than that in miR-NC group at 1 h and 8 h after irradiation (P<0.05).Conclusion:miR-34s are radioresponsive miRNA molecules,and overexpression of miR-34s can increase the level of ionizing radiation-induced DNA damage and enhance the radiosensitivity of CRC cells.

References:

[1] HYUNA SUNG,JACQUES FERLAY,REBECCA L SIEGEL,et al.Global cancer statistics 2020:GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J].CA Cancer J Clin,2021,71(3):209-249.
[2] ZHANG N,HU X,DU Y,et al.The role of miRNAs in colorectal cancer progression and chemoradiotherapy[J].Biomed Pharmacother,2021,134(2):111099.
[3] LU TX,ROTHENBERG ME.MicroRNA[J].J Allergy Clin Immunol,2018,141(4):1202-1207.
[4] ZHANG L,LIAO Y,TANG L.MicroRNA-34 family:a potential tumor suppressor and therapeutic candidate in cancer[J].J Exp Clin Cancer Res,2019,38(1):53.
[5] HOSSEINAHLI N,AGHAPOUR M,DUIJF PHG,et al.Treating cancer with microRNA replacement therapy:A literature review[J].J Cell Physiol,2018,233(8):5574-5588.
[6] ZHENG R,LIU Y,ZHANG X,et al.miRNA-200c enhances radiosensitivity of esophageal cancer by cell cycle arrest and targeting P21[J].Biomed Pharmacother,2017,90(6):517-523.
[7] ZHANG T,XUE X,PENG H.Therapeutic delivery of miR-29b enhances radiosensitivity in cervical cancer[J].Mol Ther,2019,27(6):1183-1194.
[8] AGOSTINI M,KNIGHT RA.miR-34:from bench to bedside[J].Oncotarget,2014,5(4):872-881.
[9] VOGT M,MUNDING J,GRNER M,et al.Frequent concomitant inactivation of miR-34a and miR-34b/c by CpG methylation in colorectal,pancreatic,mammary,ovarian,urothelial,and renal cell carcinomas and soft tissue sarcomas[J].Virchows Arch,2011,458(3):313-322.
[10] LODYGIN D,TARASOV V,EPANCHINTSEV A,et al.Inactivation of miR-34a by aberrant CpG methylation in multiple types of cancer[J].Cell Cycle,2008,7(16):2591-2600.
[11] ROKAVEC M,LI H,JIANG L,et al.The p53/miR-34 axis in development and disease[J].J Mol Cell Biol,2014,6(3):214-230.
[12] GAO X,SAHA D,KAPUR P,et al.Radiosensitization of HT-29 cells and xenografts by the nitric oxide donor DETANONOate[J].J Surg Oncol,2009,100(2):149-158.
[13] GANDELLINI P,RANCATI T,VALDAGNI R,et al.miRNAs in tumor radiation response:bystanders or participants[J].Trends Mol Med,2014,20(9):529-539.
[14] PRICE JM,PRABHAKARAN A,WEST CML.Predicting tumour radiosensitivity to deliver precision radiotherapy[J].Nat Rev Clin Oncol,2023,20(2):83-98.
[15] BUCKLEY AM,LYNAM-LENNON N,O' NEILL H,et al.Targeting hallmarks of cancer to enhance radiosensitivity in gastrointestinal cancers[J].Nat Rev Gastroenterol Hepatol,2020,17(5):298-313.
[16] MISSO G,DI MARTINO MT,DE ROSA G,et al.Mir-34:a new weapon against cancer[J].Mol Ther Nucleic Acids,2014,3(9):e194.
[17] CHEN S,LIU R,WANG Q,et al.MiR-34s negatively regulate homologous recombination through targeting RAD51[J].Arch Biochem Biophys,2019,666(6):73-82.
[18] HERMEKING H.The miR-34 family in cancer and apoptosis[J].Cell Death Differ,2010,17(2):193-199.
[19] RUPAIMOOLE R,SLACK FJ.MicroRNA therapeutics:towards a new era for the management of cancer and other diseases[J].Nat Rev Drug Discov,2017,16(3):203-222.
[20] BEG MS,BRENNER AJ,SACHDEV J,et al.Phase I study of MRX34,a liposomal miR-34a mimic,administered twice weekly in patients with advanced solid tumors[J].Invest New Drugs,2017,35(2):180-188.
[21] HONG DS,KANG YK,BORAD M,et al.Phase 1 study of MRX34,a liposomal miR-34a mimic,in patients with advanced solid tumours[J].Br J Cancer,2020,122(11):1630-1637.

Memo

Memo:
军队后勤科研面上项目(编号:CEP21J010)
Last Update: 1900-01-01