Abstract:Objective: To explore the mechanism of SNHG15-lncRNA ceRNA network to promote glioma proliferation by targeting miR-451a. Methods: The expression levels of SNHG15 and miR-451a in clinical tissue samples, human glial cell lines HEB, and glioma cell lines (U87, U251 and Hs683) were detected by qRT-PCR. Dual luciferase reporter gene assay, qRT-PCR and Pull down were used to detect the targeted regulation of SNHG15-miR-451a axis. U87 cells were transfected with SNHG15 small interfering RNA (siRNA), negative control sequence (NC) and miR-451a inhibitor. The cells were randomly divided into siNC group, siSNHG15 group and siSNHG15+miR-451a inhibitor group. The regulation of invasion, migration and apoptosis of U87 cells by SNHG15 and miR-451a were detected by Transwellcell invasion, cell scratching and Tunel cell apoptosis, respectively. A subcutaneous transplantation tumor model of glioma in nude mice was constructed to detect tumor growth and cell proliferation in vivo. Results: Compared with the adjacent tissues and HEB cells, the expression of SNHG15 in glioma tissues and glioma cell lines was significantly increased, while the expression of miR-451a was significantly decreased (all P<0.05). Dual luciferase reporter gene results showed that SNHG15 luciferase activity increased significantly after transfection with miR-451a inhibitor (P<0.05). Pull down biotinylation assay showed that miR-451a decreased the expression level of SNHG15 in U87 cells (p<0.05), while the expression of miR-451a was decreased after transfection with SNHG15 plasmid (P<0.05). SNHG15 significantly inhibited, while miR-451a inhibitor significantly promoted the invasion, migration distance and apoptosis rate of U87 cells (all P<0.05). The SNHG15 group had a significantly higher graft weight than the NC group, while the miR-451a group had a significantly lower graft weight than the miR-NC group (both P<0.05) The expression of PCNA in siSNHG15 group was lower than in siNC group and siSNHG15+miR-451a inhibitor group (both P<0.05). The expression of PCNA in miR-451a inhibitor group was higher than in NC inhibitor group and siSNHG15+miR-451a inhibitor group (all P<0.05). Conclusions: SNHG15 competitively binds miR-451a to promotes the invasion and migration of glioma cell, and inhibits apoptosis. Down-regulating the SNHG15-miR-451a axis might serve as a new therapeutic target for glioma treatment.
[1] Han Y,Sun Y,Zhang Y,et al.High DPP4 expression predicts poor prognosis in patients with low-grade glioma[J].Mol Biol Rep,2020,47(3):2189~2196. [2] Liu ZZ,Tian YF,Wu H,et al.LncRNA H19 promotes glioma angiogenesis through miR-138/HIF-1α/VEGF axis[J].Neoplasma,2020,67(1):111~118. [3] Mu M,Niu W,Zhang X,et al.LncRNA BCYRN1 inhibits glioma tumorigenesis by competitively binding with miR-619-5p to regulate CUEDC2 expression and the PTEN/AKT/p21 pathway[J].Oncogene,2020,39(45):6879~6892. [4] Liu Y,Li J,Li F,et al.SNHG15 functions as a tumor suppressor in thyroid cancer[J].Cell Biochem,2019,120(4):6120~6126. [5] Luan F,Chen W,Chen M,et al.An autophagy-related long non-coding RNA signature for glioma[J].FEBS Open Bio,2019,9(4):653~667. [6] Li M,Bian Z,Jin G,et al.LncRNA-SNHG15 enhances cell proliferation in colorectal cancer by inhibiting miR-338-3p[J].Cancer Med,2019,8(5):2404~2413. [7] Dong YZ,Meng XM,Li GS.Long non-coding RNA SNHG15 indicates poor prognosis of non-small cell lung cancer and promotes cell proliferation and invasion[J].Eur Rev Med Pharmacol Sci,2018,22(9):2671~2679. [8] Li Z,Zhang J,Zheng H,et al.Modulating lncRNA SNHG15/CDK6/miR-627 circuit by palbociclib,overcomes temozolomide resistance and reduces M2-polarization of glioma associated microglia in glioblastoma multiforme[J].Exp Clin Cancer Res,2019,38(1):380. [9] Xin J,Zhao YH,Zhang XY,et al.LncRNA NFIA-AS2 promotes glioma progression through modulating the miR-655-3p/ZFX axis[J].Hum Cell,2020,33(4):1273~1280. [10] Huang W,Shi Y,Han B,et al.LncRNA GAS5-AS1 inhibits glioma proliferation,migration and invasion via miR-106b-5p/TUSC2 axis[J].Hum Cell,2020,33(2):416~426.