MicroRNA-4530 suppresses cell proliferation and induces apoptosis by targeting RASA1 in human umbilical vein endothelial cells

被引:11
作者
Jing, Li [1 ]
Li, Hong [1 ]
Zhang, Tao [1 ]
Lu, Jianxin [1 ]
Zhong, Lianjin [1 ]
机构
[1] Wenzhou Med Univ, Coll Lab Med & Life Sci, Zhejiang Prov Key Lab Med Genet, Key Lab Lab Med,Minist Educ, Tongde Bldg,268 Coll West Rd, Wenzhou 325035, Zhejiang, Peoples R China
关键词
microRNA-4530; Ras GTPase-activating protein 1; human umbilical vein endothelial cells; proliferation; apoptosis; DIFFERENTIAL EXPRESSION; PROMOTES ANGIOGENESIS; DIABETIC-RETINOPATHY; CANCER-CELLS; TUMOR-GROWTH; PATHWAY; PROGRESSION; TRANSLATION; INHIBITION; ACTIVATION;
D O I
10.3892/mmr.2019.10000
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
MicroRNAs (miRNAs/miRs) are a class of endogenous and non-coding RNAs that are present in eukaryotes. In previous studies, miRNAs have been revealed to have an important role in cell growth and apoptosis. In the present study, the function of a novel and rarely studied miRNA, miR-4530, was investigated in human umbilical vein endothelial cells (HUVECs). The expression level of miR-4530 in HUVECs was investigated using reverse transcription-quantitative polymerase chain reaction following transfection with miR-4530 precursor plasmids, anti-miR-4530 plasmids and empty vector plasmids. Following this, it was revealed that overexpression of miR-4530 can suppress cell proliferation and enhance cell apoptosis. TargetScan analysis suggested that Ras p21 protein activator 1 (RASA1) is a target gene of miR-4530. The results of a dual-luciferase reporter assay also suggested that miR-4530 targets RASA1. Furthermore, the results of dual-luciferase reporter assay suggested that miR-4530 enhanced luciferase activity of the wild-type reporter, but not the mutant RASA1 reporter activity, thus suggesting that miR-4530 enhances the expression of RASA1. In addition, western blot analysis demonstrated that the protein expression level of RASA1 was enhanced following upregulation of miR-4530. The exact mechanism underlying this process has not yet been determined and requires further investigation. In addition, a RASA1 overexpression plasmid vector was transfected into HUVECs. The results suggest that overexpression of RASA1 suppresses cell growth and promotes apoptosis, which was in agreement with the results regarding the overexpression of miR-4530. To investigate how miRNA-4530 affects cellular function, numerous proteins associated with the extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K)/AKT serine/threonine kinase pathways were investigated via western blot analysis. The results suggested that miRNA-4530 suppresses cell proliferation and enhances apoptosis by targeting RASA1 via the ERK/MAPK and PI3K/AKT signaling pathways.
引用
收藏
页码:3393 / 3402
页数:10
相关论文
共 42 条
  • [1] [Anonymous], OPEN CANC J, DOI DOI 10.2174/1874079001003010055
  • [2] 1GF-1 receptor-mediated ERK/MAPK signaling couples status epilepticus to progenitor cell proliferation in the subgranular layer of the dentate gyrus
    Choi, Yun-Sik
    Cho, Hee-Yeon
    Hoyt, Kari R.
    Naegele, Janice R.
    Obrietan, Karl
    [J]. GLIA, 2008, 56 (07) : 791 - 800
  • [3] miR-145 and miR-143 regulate smooth muscle cell fate and plasticity
    Cordes, Kimberly R.
    Sheehy, Neil T.
    White, Mark P.
    Berry, Emily C.
    Morton, Sarah U.
    Muth, Alecia N.
    Lee, Ting-Hein
    Miano, Joseph M.
    Ivey, Kathryn N.
    Srivastava, Deepak
    [J]. NATURE, 2009, 460 (7256) : 705 - U80
  • [4] Identification of the differential expression of serum microRNA in type 2 diabetes
    Ding, Linchao
    Ai, Dongdong
    Wu, Ruihao
    Zhang, Tao
    Jing, Li
    Lu, Jianxin
    Zhong, Lianjin
    [J]. BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY, 2016, 80 (03) : 461 - 465
  • [5] Hypoxia-inducible MiR-182 promotes angiogenesis by targeting RASA1 in hepatocellular carcinoma
    Du, Chengli
    Weng, Xiaoyu
    Hu, Wendi
    Lv, Zhen
    Xiao, Heng
    Ding, Chaofeng
    Gyabaah, Owusu-anash K.
    Xie, Haiyang
    Zhou, Lin
    Wu, Jian
    Zheng, Shusen
    [J]. JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH, 2015, 34
  • [6] Funatsu Hideharu, 1993, Nippon Ganka Gakkai Zasshi, V97, P939
  • [7] MiR-21/RASA1 axis affects malignancy of colon cancer cells via RAS pathways
    Gong, Bo
    Liu, Wan-Wei
    Nie, Wen-Jing
    Li, Dong-Feng
    Xie, Zi-Jun
    Liu, Chao
    Liu, Yan-Hui
    Mei, Ping
    Li, Zi-Jun
    [J]. WORLD JOURNAL OF GASTROENTEROLOGY, 2015, 21 (05) : 1488 - 1497
  • [8] MicroRNA-101 inhibits cell proliferation and induces apoptosis by targeting EYA1 in breast cancer
    Guan, Haitao
    Dai, Zhijun
    Ma, Yuguang
    Wang, Zhongwei
    Liu, Xiaoxu
    Wang, Xijing
    [J]. INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE, 2016, 37 (06) : 1643 - 1651
  • [9] Guangda L, 2005, J CLIN OPHTHALMOL, V13, P381
  • [10] Occurrence and progression of diabetic retinopathy after phacoemulsification cataract surgery
    Hauser, D
    Katz, H
    Pokroy, R
    Bukelman, A
    Shechtman, E
    Pollack, A
    [J]. JOURNAL OF CATARACT AND REFRACTIVE SURGERY, 2004, 30 (02) : 428 - 432