microRNA miR-10b inhibition reduces cell proliferation and promotes apoptosis in non-small cell lung cancer (NSCLC) cells

被引:61
作者
Huang, Junchao [1 ]
Sun, Chengchao [2 ]
Wang, Suqing [2 ]
He, Qiqiang [2 ]
Li, Dejia [2 ]
机构
[1] Hubei Univ Sci & Technol, Hubei Prov Key Lab Cardiovasc Cerebrovasc & Metab, Sch Nucl Technol & Chem & Biol, Xianning 437100, Peoples R China
[2] Wuhan Univ, Global Hlth Inst, Sch Publ Hlth, Wuhan 430071, Peoples R China
基金
中国国家自然科学基金;
关键词
KLOTHO; INVASION; GROWTH; PROFILES; MOUSE;
D O I
10.1039/c4mb00752b
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Lung cancer is one of the most common and serious types of cancer. Till now, the treatment of lung cancer has been unsatisfactory, which is associated with poor prognosis and high mortality. Therefore, there is an urgent requirement to investigate the molecular mechanisms underlying lung tumorigenesis. To study the potential function of miR-10b involved in the regulation of lung tumors, we monitored NSCLC cell behaviour including proliferation, apoptosis and cell cycle using CCK-8 and flow cytometry analysis. Real-time PCR was used to detect the expression levels of miR-10b in 75 NSCLC patients' tissues and Western blot was also used to analyze the expression level of genes correlated with apoptosis in NSCLC cells. miR-10b expression levels were higher in NSCLC tissues compared with an adjacent normal tissue control. Silencing of miR-10b inhibited cancer cell progress by arresting cell cycle progression in the G0/G1 phase and promoted apoptosis in NSCLC cells. Western blot analysis of miR-10b-silenced cells revealed up-regulation of apoptosis-inducing members Fas, FasL, Bax and caspase 3, and down-regulation of apoptosis-inhibiting factors Bcl-2 and PCNA. And, a significant inverse correlation between the level of miR-10b and klotho was observed, which has been demonstrated to be a novel tumor suppressor gene. A further in vivo tumor formation study in nude mice indicated that inhibition of miR-10b in lung cancer cells delayed the progress of tumor formation. These findings indicated that miR-10b might serve as a useful potential target for treatment of NSCLC.
引用
收藏
页码:2051 / 2059
页数:9
相关论文
共 30 条
  • [1] Epidemiology of lung cancer - ACCP evidence-based clinical practice guidelines (2nd edition)
    Alberg, Anthony J.
    Ford, Jean G.
    Samet, Jonathan M.
    [J]. CHEST, 2007, 132 (03) : 29S - 55S
  • [2] MicroRNAs: Novel Biomarkers for Human Cancer
    Bartels, Claudine L.
    Tsongalis, Gregory J.
    [J]. CLINICAL CHEMISTRY, 2009, 55 (04) : 623 - 631
  • [3] Klotho inhibits the capacity of cell migration and invasion in cervical cancer
    Chang, Boogi
    Kim, Jinsun
    Jeong, Dongjun
    Jeong, Yujun
    Jeon, Seob
    Jung, Sam-Il
    Yang, Young
    Kim, Keun Il
    Lim, Jong-Seok
    Kim, Changjin
    Lee, Myeong-Sok
    [J]. ONCOLOGY REPORTS, 2012, 28 (03) : 1022 - 1028
  • [4] Inhibition of lung cancer cells growth, motility and induction of apoptosis by Klotho, a novel secreted Wnt antagonist, in a dose-dependent manner
    Chen, Bo
    Ma, Xiaoli
    Liu, Shifeng
    Zhao, Weihong
    Wu, Jianqing
    [J]. CANCER BIOLOGY & THERAPY, 2012, 13 (12) : 1221 - 1228
  • [5] Klotho inhibits growth and promotes apoptosis in human lung cancer cell line A549
    Chen, Bo
    Wang, Xueli
    Zhao, Weihong
    Wu, Jianqing
    [J]. JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH, 2010, 29
  • [6] Causes and consequences of microRNA dysregulation in cancer
    Croce, Carlo M.
    [J]. NATURE REVIEWS GENETICS, 2009, 10 (10) : 704 - 714
  • [7] miRNAs in human cancer
    Farazi, Thalia A.
    Spitzer, Jessica I.
    Morozov, Pavel
    Tuschl, Thomas
    [J]. JOURNAL OF PATHOLOGY, 2011, 223 (02) : 102 - 115
  • [8] Human Glioma Growth Is Controlled by MicroRNA-10b
    Gabriely, Galina
    Yi, Ming
    Narayan, Ravi S.
    Niers, Johanna M.
    Wurdinger, Thomas
    Imitola, Jaime
    Ligon, Keith L.
    Kesari, Santosh
    Esau, Christine
    Stephens, Robert M.
    Tannous, Bakhos A.
    Krichevsky, Anna M.
    [J]. CANCER RESEARCH, 2011, 71 (10) : 3563 - 3572
  • [9] Mutations and addiction to EGFR:: the Achilles 'heal' of lung cancers?
    Gazdar, AF
    Shigematsu, H
    Herz, J
    Minna, JD
    [J]. TRENDS IN MOLECULAR MEDICINE, 2004, 10 (10) : 481 - 486
  • [10] Cancer statistics, 2007
    Jemal, Ahmedin
    Siegel, Rebecca
    Ward, Elizabeth
    Murray, Taylor
    Xu, Jiaquan
    Thun, Michael J.
    [J]. CA-A CANCER JOURNAL FOR CLINICIANS, 2007, 57 (01) : 43 - 66