MiR-296 regulation of a cell polarity-cell plasticity module controls tumor progression

Division of Pathology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
Oncogene (Impact Factor: 8.56). 06/2011; 31(1):27-38. DOI: 10.1038/onc.2011.209
Source: PubMed

ABSTRACT The expression of small, non-coding RNA, or microRNAs (miR), is frequently deregulated in human cancer, but how these pathways affect disease progression is still largely elusive. Here, we report on a microRNA, miR-296, which is progressively lost during tumor progression, and correlates with metastatic disease in colorectal, breast, lung, gastric, parathyroid, liver and bile ducts cancers. Functionally, miR-296 controls a global cell motility gene signature in epithelial cells by transcriptionally repressing the cell polarity-cell plasticity module, Scrib. In turn, loss of miR-296 causes aberrantly increased and mislocalized Scrib in human tumors, resulting in exaggerated random cell migration, and tumor cell invasiveness. Re-expression of miR-296 in MDA-MB231 cells inhibits tumor growth, in vivo. Finally, miR-296 or Scrib levels predict tumor relapse in hepatocellular carcinoma patients.
These data identify miR-296 as a global repressor of tumorigenicity, and uncover a previously unexplored exploitation of Scrib in tumor progression in humans.

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Available from: Valentina Vaira, Aug 31, 2015
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    • "Each step was performed at room temperature. Neoplastic lesions were isolated and separated from the normal lung tissue using the LMD 6000 system (Leica Microsystems), as previously described [23]. Microdissected samples were collected into the cap of 0.2-ml microcentrifuge tubes and stored at 4°C. "
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    • "Promotes proliferation and inhibits apoptosis inhibitor-5 (API-5) transcript expression Murakami et al., 2006; Meng et al., 2007; Gramantieri et al., 2008; Ladeiro et al., 2008; Li et al., 2008; Wang et al., 2008; Chen, 2009; Huang et al., 2009; Liu et al., 2009; Su et al., 2009; Pineau et al., 2010; Wong et al., 2010 miR-296-5p It is still unknown if contribute to HCC development and tumor progression Borel et al., 2012b; Katayama et al., 2012; Vaira et al., 2012; Wei et al., 2013b miR-338/-3p Associated with clinical HCC aggressiveness. Stimulation of HCC proliferation Budhu et al., 2008; Gramantieri et al., 2008; Huang et al., 2009, 2011 miR-373 Invasion and metastasis Meng et al., 2007; Bartels and Tsongalis, 2009; Wu et al., 2011 miR-374 Development Wang et al., 2008; Wong et al., 2008, 2010; Koh et al., 2013 miR-375 Stimulation of HCC proliferation Liu et al., 2010; He et al., 2012 miR-376a Proliferation and apoptosis Meng et al., 2007; Zheng et al., 2012b miR-423 Enhanced CDK2 activity Lin et al., 2011 miR-491-5p Inhibition of TNF-α-related apoptosis Yoon et al., 2010 miR-500 Elevated in HCC, returned to physiologic level after surgical intervention Yamamoto et al., 2009 miR-637 Active STAT3 Zhang et al., 2011 let-7a/a-1/a- 2/b/c/d/e/f/f-2/g Development. "
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