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- 2017
miR-498通过下调FOXM1抑制肺腺癌细胞系A549的迁移侵袭
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Abstract:
摘要:目的 探索微小RNA498(miR-498)是否通过下调FOXM1抑制肺癌细胞系(A549)细胞的迁移和侵袭。方法 转染miR-498mimic和miR-NC至培养的A549细胞中,Western blot检测A549细胞中COL1A1、COL1A5、FOXM1的表达情况,划痕试验和Transwell法观察细胞迁移侵袭情况,荧光素酶试验验证FOXM1是miR-498的靶基因;再通过转染过表达FOXM1的质粒至已成功转染miR-498的A549细胞中,检测A549细胞中COL1A1、COL1A5、FOXM1的表达情况,划痕试验和Transwell法观察细胞迁移侵袭情况。结果 与空质粒组比较,转染miR-498mimic的A549细胞中COL1A1、COL1A5、FOXM1的表达减少(P<0.05),A549细胞的迁移侵袭减少(P<0.01);荧光素酶实验结果显示,miR-498能够显著降低FOXM1-3′-UTR质粒的荧光素活性(P<0.05);与miR-498+空质粒组比较,转染过表达FOXM1质粒的A549细胞中COL1A1、COL1A5表达增加(P<0.05),细胞的迁移侵袭增加(P<0.01)。 结论 miR-498可以通过下调FOXM1而抑制A549的迁移和侵袭。
ABSTRACT: Objective To verify whether miR-498 can inhibit A549 cell migration and invasion by down-regulating FOXM1. Methods miR-498 mimic and miR-NC were transfected into A549 cells. Wound healing and Transwell method were employed to test the migratory ability and invasion ability of A549 cells; Western blot was used to detect the expressions of COL1A1, COL1A5 and FOXM1 in A549 cells. Luciferase assay was used to confirm whether FOXM1 is the target gene of miR-498. Results Compared with those in the control group, the expressions of COL1A1, COL1A5 and FOXM1 were decreased, and the migration and invasion abilities of A549 cells were decreased in the miR-498 group (both P<0.01). The luciferase activity of the FOXM1-3′-UTR plasmid was significantly suppressed by miR-498 (P<0.05); over-expression of FOXM1 could reverse the effect of miR-498 on A549 cells. Conclusion miR-498 inhibits A549 cell migration and invasion by down-regulating FOXM1
[1] | WANG M, ZHANG Q, WANG J, et al. MicroRNA-498 is downregulated in non-small cell lung cancer and correlates with tumor progression[J]. J Cancer Res Ther, 2015, 11(Suppl 1):C107-111. |
[2] | GRIGOROIU M, TAGETT R, DRAGHICI S, et al. Gene-expression profiling in non-small cell lung cancer with invasion of mediastinal lymph nodes for prognosis evaluation[J]. Cancer Genomics Proteomics, 2015, 12(5):231-242. |
[3] | 2016, 155:155-160. |
[4] | BAO B, WANG Z, ALI S, et al. Over-expression of FoxM1 leads to epithelial-mesenchymal transition and cancer stem cell phenotype in pancreatic cancer cells[J]. J Cell Biochem, 2011, 112(9):2296-2306. |
[5] | SONG IS, JEONG YJ, JEONG SH, et al. FOXM1-induced PRX3 regulates stemness and survival of colon cancer cells via maintenance of mitochondrial function[J]. Gastroenterology, 2015, 149(4):1006-1016.e1009. |
[6] | GU C, YANG Y, SOMPALLAE R, et al. FOXM1 is a therapeutic target for high-risk multiple myeloma[J]. Leukemia, 2016, 30(4):873-882. |
[7] | GOPALAN V, SMITH RA, LAM AK. Downregulation of microRNA-498 in colorectal cancers and its cellular effects[J]. Exp Cell Res, 2015, 330(2):423-428. |
[8] | LIU R, LIU F, LI L, et al. MiR-498 regulated FOXO3 expression and inhibited the proliferation of human ovarian cancer cells[J]. Biomed Pharmacother, 2015, 72:52-57. |
[9] | JIA J, FENG X, XU W, et al. MiR-17-5p modulates osteoblastic differentiation and cell proliferation by targeting SMAD7 in non-traumatic osteonecrosis[J]. Exp Mol Med, 2014, 46:e107. |
[10] | BAIG MS, SAQIB U, SHAH VH. Non-canonical role of matrix metalloprotease (MMP) in activation and migration of hepatic stellate cells (HSCs)[J]. Life Sci, |
[11] | HOU Y, LI W, SHENG Y, et al. The transcription factor Foxm1 is essential for the quiescence and maintenance of hematopoietic stem cells[J]. Nat Immunol, 2015, 16(8):810-818. |
[12] | AYTES A, MITROFANOVA A, LEFEBVRE C, et al. Cross-species regulatory network analysis identifies a synergistic interaction between FOXM1 and CENPF that drives prostate cancer malignancy[J]. Cancer Cell, 2014, 25(5):638-651. |
[13] | TAN X, FU Y, CHEN L, et al. miR-671-5p inhibits epithelial-to-mesenchymal transition by downregulating FOXM1 expression in breast cancer[J]. Oncotarget, 2016, 7(1):293-307. |
[14] | MATAMALA N, VARGAS MT, GONZALEZ-CAMPORA R, et al. MicroRNA deregulation in triple negative breast cancer reveals a role of miR-498 in regulating BRCA1 expression[J]. Oncotarget, 2016, 7(15):20068-20079. |
[15] | YIO X, DIAMOND M, ZHANG JY, et al. Trefoil factor family-1 mutations enhance gastric cancer cell invasion through distinct signaling pathways[J]. Gastroenterology, 2006, 130(6):1696-1706. |
[16] | ZHOU CX, WANG CL, YU AL, et al. MiR-630 suppresses breast cancer progression by targeting metadherin[J]. Oncotarget, 2016, 7(2):1288-1299. |
[17] | CAO JX, LU Y, QI JJ, et al. MiR-630 inhibits proliferation by targeting CDC7 kinase, but maintains the apoptotic balance by targeting multiple modulators in human lung cancer A549 cells[J]. Cell Death Dis, 2014, 5:e1426. |
[18] | YAN Q, LI W, TANG Q, et al. Cellular microRNAs 498 and 320d regulate herpes simplex virus 1 induction of Kaposi??s sarcoma-associated herpesvirus lytic replication by targeting RTA[J]. PLoS One, 2013, 8(2):e55832. |
[19] | FENG Y, WANG L, ZENG J, et al. FoxM1 is overexpressed in Helicobacter pylori-induced gastric carcinogenesis and is negatively regulated by miR-370[J]. Mol Cancer Res, 2013, 11(8):834-844. |
[20] | 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 Lett, 2014, 588(17):3170-3179. |