Abstract:Objective: To analyze the effects of microRNA-105-5p (miR-105-5p) on the proliferation and migration of glioma cells by regulating cell division cycle 5-like protein (CDC5L). Methods: Samples of 35 surgically treated human glioma tissues and normal brain tissues undergoing decompression due to traumatic brain injury were collected from our hospital. Logarithmic growth phase U251 cells were divided into control (control) group, transfected miR-105-5p negative control (miR-NC) group, transfected miR-105-5p mimics (miR-105-5p mimics) group, transfected silent CDC5L negative control (si-NC) group, transfected silent CDC5L (si-CDC5L) group , co-transfected miR-105-5p mimics and pcDNA (pcDNA) group, and co-transfected miR-105-5p mimics and pcDNA-CDC5L (miR-105-5p mimics+pcDNA-CDC5L) group. qRT-PCR was performed to measure the expression of miR-105-5p and CDC5L mRNA in glioma tissue, normal brain tissue, and U251 cells in each group; CCK-8 method was performed to measure cell proliferation; Transwell was performed to measure cell migration; Western blot method was performed to measure the expression of CDC5L, CyclinDl, matrix metalloproteinase 2 (MMP-2), MMP-9 and cyclin-dependent kinase inhibitor 1A (p21); dual luciferase reporter assay validated the targeting of miR-105-5p to CDC5L Results: Compared with normal brain tissue, the level of miR-105-5p in glioma tissue was significantly decreased,and CDC5L mRNA was significantly increased; miR-105-5p was negatively correlated with CDC5L (r= -0.512,P=0.002). Compared with the control group and si-NC group, the expression of p21 protein was increased in the si-CDC5L group (P<0.05), and the OD values at 24h, 48h and 72h, the number of migrating cells, the expression of CDC5L mRNA and the expression of CDC5L, CyclinDl, MMP-2 and MMP-9 proteins were decreased (P<0.05). Compared with the control group and miR-NC group, the expression of miR-105-5p and p21 protein was increased in the miR-105-5p mimics group (P<0.05), and the OD values at 24h, 48h and 72h, the number of migrating cells, the expression of CDC5L mRNA and the expression of CDC5L, CyclinDl, MMP-2 and MMP-9 proteins were decreased (P<0.05). Overexpression of CDC5L was able to reverse the effects of miR-105-5p on the proliferation and migration of U251 cells and CyclinDl, MMP-2, MMP-9, and p21 proteins (P<0.05); the dual luciferase experiment verified that CDC5L was the downstream target of miR-105-5p. Conclusion: miR-105-5p inhibits the proliferation and migration of glioma cells by down-regulating CDC5L.
宋海龙, 徐东为, 余秋男, 荆彦平, 李世冲, 刘建中, 刘京让. miR-105-5p调控CDC5L表达对胶质瘤细胞增殖迁移的影响[J]. 河北医学, 2023, 29(6): 906-911.
SONG Hailong, XU Dongwei, YU Qiunan, et al. Effects of miR-105-5p Regulating the Expression of CDC5L on Proliferation and Migration of Glioma Cells. HeBei Med, 2023, 29(6): 906-911.
[1] 莫文澜,张琳,金必莲,等.EZH2在脑胶质瘤发生发展中作用机制研究进展[J].中华肿瘤防治杂志,2022,29(24):1768-1778.. [2] Tom MC,Cahill DP,Buckner JC,et al.Management for different glioma subtypes:are all low-grade gliomas created equal[J].Am Soc Clin Oncol Educ Book,2019,39(1):133-145. [3] Khan AQ,Ahmed EI,Elareer NR,et al.Role of miRNA-regulated cancer stem cells in the pathogenesis of human malignancies[J].Cells,2019,8(8):840-872. [4] Wei S,Liu K,He Q,et al.PES1 is regulated by CD44 in liver cancer stem cells via miR-105-5p[J].FEBS Lett,2019,593(14):1777-1786. [5] 蔡元霞,武志祥,王奕,等.CDC5L表达对神经母细胞瘤临床及预后评估的意义[J].临床小儿外科杂志,2019,18(6):472-479. [6] Bilmin K,Kujawska T,Grieb P.Sonodynamic therapy for gliomas.perspectives and prospects of selective sonosensitization of glioma cells[J].Cells,2019,8(11):1428-1438. [7] Haider AS,van den Bent M,Wen PY,et al.Toward a standard pathological and molecular characterization of recurrent glioma in adults:a response assessment in neuro-oncology effort[J].Neuro Oncol,2020,22(4):450-456. [8] Wang S,Yin Y,Liu S.Roles of microRNAs during glioma tumorigenesis and progression[J].Histol Histopathol,2019,34(3):213-222. [9] Miliotis C,Slack FJ.miR-105-5p regulates PD-L1 expression and tumor immunogenicity in gastric cancer[J].Cancer Lett,2021,518(1):115-126. [10] 李耀杰,汤素娜,王保收,等.miR-105-5p靶向MAPK1抑制非小细胞肺癌细胞A549的生长、运动和上皮间质转化[J].中国免疫学杂志,2020,36(20):2485-2490. [11] Suo ST,Gong P,Peng XJ,et al.Knockdown of long non-coding RNA VIM-AS1 inhibits glioma cell proliferation and migration,and increases the cell apoptosis via modulation of WEE1 targeted by miR-105-5p[J].Eur Rev Med Pharmacol Sci,2020,24(12):6834-6847. [12] Liu H,Guo D,Sha Y,et al.ANXA7 promotes the cell cycle,proliferation and cell adhesion-mediated drug resistance of multiple myeloma cells by up-regulating CDC5L[J].Aging (Albany NY),2020,12(11):11100-11115. [13] Wang K,Li B,Fan P,et al.Downregulation of DEAD-box helicase 21 (DDX21) inhibits proliferation,cell cycle,and tumor growth in colorectal cancer via targeting cell division cycle 5-like (CDC5L)[J].Bioengineered,2021,12(2):12647-12658. [14] Zhang Z,Mao W,Wang L,et al.Depletion of CDC5L inhibits bladder cancer tumorigenesis[J].Cancer,2020,11(2):353-363. [15] Chen W,Zhang L,Wang Y,et al.Expression of CDC5L is associated with tumor progression in gliomas[J].Tumour Biol,2016,37(3):4093-103.