[an error occurred while processing this directive] | [an error occurred while processing this directive]
Silencing lncRNA UCA1 affects radiosensitivity of glioma cells by up-regulating miR-873-5p expression
Yuan Jinjin1, Liu Zongwen1, Song Rui1, Liu Junqi2, Fan Ruitai2
1Department of Radiation Oncology, Second Affiliated Hospital of Zhengzhou University, Zhengzhou 450014, China; 2Department of Radiation Oncology, Frist Affiliated Hospital of Zhengzhou University, Zhengzhou 450003, China
AbstractObjective To investigate the effect of lncRNA UCA1 on the radiosensitivity of in vitro cultured glioma cell lines SHG-44, U87 and U251 by regulating the miR-873-5p expression. Methods The survival of glioma cells SHG-44, U87 and U251 treated with different radiation intensities (0, 2, 4, 6 and 8Gy) was detected by colony formation assay. The expression levels of UCA1 in glioma cells SHG-44, U87 and U251 were measured by qRT-PCR. The radiation-resistant glioma cells U87 and U251 were selected for subsequent study. After silencing UCA1 expression and/or over-expressing miR-873-5p, the cell survival rate was detected by colony formation assay, and the cell apoptosis rate was determined by flow cytometry. The dual luciferase reporter gene assay and qRT-PCR were employed to verify the targeting relationship between UCA1 and miR-873-5p. Results UCA1 was up-regulated in the radiation-resistant U87 and U251 cells. Silencing UCA1 or over-expressing miR-873-5p inhibited the survival of U87 and U251 cells, and promoted the cell apoptosis induced by radiation exposure. miR-873-5p was a target gene of UCA1, and UCA1 negatively regulated the expression of miR-873-5p. The inhibition of miR-873-5p could reverse the effect of silencing UCA1 on the radiosensitivity of glioma cells. Silencing UCA1 increased the inhibitory effect of radiation on the glioma cell U251 xenografts. Conclusion Silencing UCA1 inhibits the survival of glioma cells and promotes the cell apoptosis by up-regulating the expression of miR-873-5p, thereby increasing the radiosensitivity of glioma cells.
[1] Vigneswaran K, Neill S, Hadjipanayis CG. Beyond the World Health Organization grading of infiltrating gliomas:advances in the molecular genetics of glioma classification[J]. Ann Transl Med, 2015, 3(7):95. DOI:10.3978/j.issn.2305-5839.2015.03.57. [2] He Z, Wang Y, Huang G, et al. The lncRNA UCA1 interacts with miR-182 to modulate glioma proliferation and migration by targeting iASPP[J]. Arch Biochem Biophys, 2017, 623-624:1-8. DOI:10.1016/j.abb.2017.01.013. [3] Sun Y, Jin JG, Mi WY, et al. Long noncoding RNA UCA1 targets miR-122 to promote proliferation, migration, and invasion of glioma cells[J]. Oncol Res, 2018, 26(1):103-110. DOI:10.3727/096504017X14934860122864. [4] Fotouhi Ghiam A, Taeb S, Huang X, et al. Long non-coding RNA urothelial carcinoma associated 1(UCA1) mediates radiation response in prostate cancer[J]. Oncotarget, 2017, 8(3):4668-4689. DOI:10.18632/oncotarget.13576. [5] Yang X, Liu W, Xu X, et al. Downregulation of long non coding RNA UCA1 enhances the radiosensitivity and inhibits migration via suppression of epithelial mesenchymal transition in colorectal cancer cells[J]. Oncol Rep, 2018, 40(3):1554-1564. DOI:10.3892/or.2018.6573. [6] 倪猛,殷涛,王旸,等. 抑制FOXD1基因表达增强结直肠癌细胞HCT116的放射敏感性[J]. 中华放射医学与防护杂志,2018, 38(12):886-893. DOI:10.3760/cma.j.issn.0254-5098.2018.12.002. Ni M, Yin T, Wang Y, et al. Suppression of FOXD1 gene expression enhances the radioactive sensitivity of HCT116 in colorectal cancer cells[J]. Chin J Radiol Med Protect, 2018,38(12):886-893. DOI:10.3760/cma.j.issn.0254-5098.2018.12.002. [7] Zheng R, Yao Q W, Ren C, et al. Upregulation of long noncoding RNA SNHG18 promotes radioresistance of glioma by repressing Sema5A[J]. Int J Radiat Oncol Biol Phys, 2016, 96(4):877-887. DOI:10.1016/j.ijrobp.2016.07.036. [8] Zheng Q, Wu F, Dai W Y, et al. Aberrant expression of UCA1 in gastric cancer and its clinical significance[J]. Clin Transl Oncol, 2015, 17(8):640-646. DOI:10.1007/s12094-015-1290-2. [9] Huang J, Zhou N, Watabe K, et al. Long non-coding RNA UCA1 promotes breast tumor growth by suppression of p27(Kip1)[J]. Cell Death Dis, 2014, 5(1):e1008. DOI:10.1038/cddis.2013.541. [10] Fang Z, Zhao J, Xie W, et al. LncRNA UCA1 promotes proliferation and cisplatin resistance of oral squamous cell carcinoma by sunppressing miR-184 expression[J]. Cancer Med, 2017, 6(12):2897-2908. DOI:10.1002/cam4.1253. [11] Ma MZ, Chu BF, Zhang Y, et al. Long non-coding RNA CCAT1 promotes gallbladder cancer development via negative modulation of miRNA-218-5p[J]. Cell Death Dis, 2015, 6(1):e1583. DOI:10.1038/cddis.2014.541. [12] Wang RJ, Li JW, Bao BH, et al. MicroRNA-873(miRNA-873) inhibits glioblastoma tumorigenesis and metastasis by suppressing the expression of IGF2bp1[J]. J Biol Chem, 2015, 290(14):8938-8948. DOI:10.1074/jbc. M114.624700. [13] Chen X, Zhang Y, Shi Y, et al. MiR-873 acts as a novel sensitizer of glioma cells to cisplatin by targeting Bcl-2[J]. Int J Oncol, 2015, 47(4):1603-1611. DOI:10.3892/ijo.2015.3143. [14] Wu DD, Li XS, Meng XN, et al. MicroRNA-873 mediates multidrug resistance in ovarian cancer cells by targeting ABCB1[J]. Tumour Biol, 2016, 37(8):10499-10506. DOI:10.1007/s13277-016-4944-y.