TITLE

MicroRNA-375 targets the 3-phosphoinositide-dependent protein kinase-1 gene in pancreatic carcinoma

AUTHOR(S)
SHI-DUO SONG; JIAN ZHOU; JIN ZHOU; HUA ZHAO; JIAN-NONG CEN; DE-CHUN LI
PUB. DATE
August 2013
SOURCE
Oncology Letters;2013, Vol. 6 Issue 4, p953
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Pancreatic carcinoma (PC) is an aggressive malignancy with one of the poorest mortality rates. It is the sixth leading cause of mortality from malignant disease in China and the fourth leading cause of cancer-related mortality in the United States. The poor outcome reflects the requirement for an improved understanding of the transcriptional control of oncogenic signaling pathways. 3-phosphoinositide-dependent protein kinase-1 (PDK1) is a potent oncogenic driver of PC. The present study aimed to elucidate the transcriptional regulation of microRNA (miR)-375-targeted PDK1. miR-375 is a putative target and, in the present study, was observed to be significantly downregulated in the tumor compared with non-tumor tissues from patients with PC (n=44). As determined by a luciferase reporter assay, the ectopic expression of miR-375 was identified to diminish the transcriptional activity of PDK1. Furthermore, immunoblotting revealed that miR-375 suppressed endogenous PDK1 protein levels. Functional assays showed that miR-375 was able to inhibit proliferation and promote apoptosis of the PC cells. miR-375 is a significant regulator of the PDK1 oncogene, suggesting that it may have a potential therapeutic role in the treatment of PC.
ACCESSION #
110397631

 

Related Articles

  • MicroRNA profiling identifies miR-129-5p as a regulator of EMT in tubular epithelial cells. Yanlin Li; Haiwen An; Jie Pang; Lin Huang; Jinshan Li; Linna Liu // International Journal of Clinical & Experimental Medicine;2015, Vol. 8 Issue 11, p20610 

    The importance of microRNAs in various diseases has been demonstrated, but their potential role in the pathogenesis of renal fibrosis needs to further research. We have profiled changes in microRNA levels in human kidney proximal tubular cell line HK-2 with TGF-β treatment and identified...

  • Erufosine suppresses breast cancer in vitro and in vivo for its activity on PI3K, c-Raf and Akt proteins. Dineva, Ilina; Zaharieva, Maya; Konstantinov, Spiro; Eibl, Hansjörg; Berger, Martin // Journal of Cancer Research & Clinical Oncology;Nov2012, Vol. 138 Issue 11, p1909 

    Purpose: This study investigated the antineoplastic effect of the membrane active alkylphosphocholine erufosine in breast carcinoma models in vitro and in vivo and determined its influence on the PI3K/Akt and Ras/Raf/MAPK signaling pathways. Methods: The antiproliferative effect of erufosine in...

  • MicroRNA-21 Regulates PI3K/Akt/mTOR Signaling by Targeting TGFβI during Skeletal Muscle Development in Pigs. Bai, Lijing; Liang, Ruyi; Yang, Yalan; Hou, Xinhua; Wang, Zishuai; Zhu, Shiyun; Wang, Chuduan; Tang, Zhonglin; Li, Kui // PLoS ONE;May2015, Vol. 10 Issue 5, p1 

    MicroRNAs (miRNAs), which are short (22–24 base pairs), non-coding RNAs, play critical roles in myogenesis. Using Solexa deep sequencing, we detected the expression levels of 229 and 209 miRNAs in swine skeletal muscle at 90 days post-coitus (E90) and 100 days postnatal (D100),...

  • MLH1 as a Direct Target of MiR-155 and a Potential Predictor of Favorable Prognosis in Pancreatic Cancer. Liu, Wen-Jing; Zhao, Yu-Pei; Zhang, Tai-Ping; Zhou, Li; Cui, Quan-Cai; Zhou, Wei-Xun; You, Lei; Chen, Ge; Shu, Hong // Journal of Gastrointestinal Surgery;Aug2013, Vol. 17 Issue 8, p1399 

    Background: The regulation of Mut L homologue 1 (MLH1) expression by microRNA (miR)-155 and its prognostic significance in pancreatic cancer (PC) remain to be elucidated. This study aimed to address the issues. Methods: MiR-155 mimics and inhibitor were transfected to PC cell lines, Panc-1 and...

  • Isoform-selective induction of human p110δ PI3K expression by TNFα: identification of a new and inducible PIK3CD promoter. WHITEHEAD, Maria A.; BOMBARDIERI, Michele; PITZALIS, Costantino; VANHAESEBROECK, Bart // Biochemical Journal;5/ 1/2012, Vol. 443 Issue 3, following p857 

    PI3Ks (phosphoinositide 3-kinases) are signalling molecules and drug targetswith important biological functions, yet the regulation of PI3K gene expression is poorly understood. Key PI3Ks are the class IA PI3Ks that consist of a catalytic subunit (p110α, p110β and p110δ) in complex with...

  • Involvement of Class II Phosphoinositide 3-Kinase α-Isoform in Antigen-Induced Degranulation in RBL-2H3 Cells. Nigorikawa, Kiyomi; Hazeki, Kaoru; Guo, Ying; Hazeki, Osamu // PLoS ONE;Oct2014, Vol. 9 Issue 10, p1 

    In this study, we present findings that suggest that PI3K-C2α, a member of the class II phosphoinositide 3-kinase (PI3K) subfamily, regulates the process of FcεRI-triggered degranulation. RBL-2H3 cells were transfected with shRNA targeting PI3K-C2α. The knockdown impaired the...

  • Phosphoinositide 3-Kinases and Leukocyte Migration. Ward, Stephen G. // Current Immunology Reviews;May2012, Vol. 8 Issue 2, p154 

    Phosphoinositide 3-kinase (PI3K) has been positioned at the heart of an evolutionarily conserved cellular compass and/or the biochemical mechanisms that facilitate cell migration. PI3K has therefore, become a popular drug target for inhibition of leukocyte migration in response to inflammatory...

  • The activation loop of PKA catalytic isoforms is differentially phosphorylated by Pkh protein kinases in Saccharomyces cerevisiae. HAESENDONCKX, Steven; TUDISCA, Vanesa; VOORDECKERS, Karin; MORENO, Silvia; THEVELEIN, Johan M.; PORTELA, Paula // Biochemical Journal;12/15/2012, Vol. 448 Issue 3, p307 

    PDK1 (phosphoinositide-dependent protein kinase 1) phosphorylates and activates PKA (cAMP-dependent protein kinase) in vitro. Docking of the HM (hydrophobic motif) in the C-terminal tail of the PKA catalytic subunits on to the PIF (PDK1-interacting fragment) pocket of PDK1 is a critical step in...

  • Differential roles for the p101 and p84 regulatory subunits of PI3Kγ in tumor growth and metastasis. Brazzatti, J A; Klingler-Hoffmann, M; Haylock-Jacobs, S; Harata-Lee, Y; Niu, M; Higgins, M D; Kochetkova, M; Hoffmann, P; McColl, S R // Oncogene;5/3/2012, Vol. 31 Issue 18, p2350 

    Phosphoinositide 3-kinase γ (PI3Kγ) consists of a catalytic subunit p110γ, which forms mutually exclusive dimers with one of the regulatory subunits called p101 and p84/p87PIKAP. Recently, PI3Kγ emerged as being a potential oncogene because overexpression of the catalytic subunit...

Share

Read the Article

Courtesy of THE LIBRARY OF VIRGINIA

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics