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Article: MicroRNA-139-5p exerts tumor suppressor function by targeting NOTCH1 in colorectal cancer

TitleMicroRNA-139-5p exerts tumor suppressor function by targeting NOTCH1 in colorectal cancer
Authors
KeywordsColorectal cancer
MiR-139-5p
NOTCH1
Tumor suppressor
Issue Date2014
Citation
Molecular Cancer, 2014, v. 13, n. 1, article no. 124 How to Cite?
AbstractBackground: miR-139-5p was identified to be significantly down-regulated in colon tumor tissues by miRNA array. We aimed to clarify its biological function, molecular mechanisms and direct target gene in colorectal cancer (CRC).Methods: The biological function of miR-139-5p was examined by cell growth, cell cycle and apoptosis analysis in vitro and in vivo. miR-139-5p target gene and signaling pathway was identified by luciferase activity assay and western blot.Results: miR-139-5p was significantly down-regulated in primary tumor tissues (P < 0.0001). Ectopic expression of miR-139-5p in colon cancer cell lines significantly suppressed cell growth as evidenced by cell viability assay (P < 0.001) and colony formation assay (P < 0.01) and in xenograft tumor growth in nude mice (P < 0.01). miR-139-5p induced apoptosis (P < 0.01), concomitantly with up-regulation of key apoptosis genes including cleaved caspase-8, caspase-3, caspase-7 and PARP. miR-139-5p also caused cell cycle arrest in G0/G1 phase (P < 0.01), with upregulation of key G0/G1 phase regulators p21Cip1/Waf1 and p27Kip1. Moreover, miR-139-5p inhibited cellular migration (P < 0.001) and invasiveness (P < 0.001) through the inhibition of matrix metalloproteinases (MMP)7 and MMP9. Oncogene NOTCH1 was revealed to be a putative target of miR-139-5p, which was inversely correlated with miR-139-5p expression (r = -0.3862, P = 0.0002).Conclusions: miR-139-5p plays a pivotal role in colon cancer through inhibiting cell proliferation, metastasis, and promoting apoptosis and cell cycle arrest by targeting oncogenic NOTCH1. © 2014 Zhang et al.; licensee BioMed Central Ltd.
Persistent Identifierhttp://hdl.handle.net/10722/336127
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorZhang, Lijing-
dc.contributor.authorDong, Yujuan-
dc.contributor.authorZhu, Nana-
dc.contributor.authorTsoi, Ho-
dc.contributor.authorZhao, Zengren-
dc.contributor.authorWu, Chung W.-
dc.contributor.authorWang, Kunning-
dc.contributor.authorZheng, Shu-
dc.contributor.authorNg, Simon S.M.-
dc.contributor.authorChan, Francis K.L.-
dc.contributor.authorSung, Joseph J.Y.-
dc.contributor.authorYu, Jun-
dc.date.accessioned2024-01-15T08:23:42Z-
dc.date.available2024-01-15T08:23:42Z-
dc.date.issued2014-
dc.identifier.citationMolecular Cancer, 2014, v. 13, n. 1, article no. 124-
dc.identifier.urihttp://hdl.handle.net/10722/336127-
dc.description.abstractBackground: miR-139-5p was identified to be significantly down-regulated in colon tumor tissues by miRNA array. We aimed to clarify its biological function, molecular mechanisms and direct target gene in colorectal cancer (CRC).Methods: The biological function of miR-139-5p was examined by cell growth, cell cycle and apoptosis analysis in vitro and in vivo. miR-139-5p target gene and signaling pathway was identified by luciferase activity assay and western blot.Results: miR-139-5p was significantly down-regulated in primary tumor tissues (P < 0.0001). Ectopic expression of miR-139-5p in colon cancer cell lines significantly suppressed cell growth as evidenced by cell viability assay (P < 0.001) and colony formation assay (P < 0.01) and in xenograft tumor growth in nude mice (P < 0.01). miR-139-5p induced apoptosis (P < 0.01), concomitantly with up-regulation of key apoptosis genes including cleaved caspase-8, caspase-3, caspase-7 and PARP. miR-139-5p also caused cell cycle arrest in G0/G1 phase (P < 0.01), with upregulation of key G0/G1 phase regulators p21Cip1/Waf1 and p27Kip1. Moreover, miR-139-5p inhibited cellular migration (P < 0.001) and invasiveness (P < 0.001) through the inhibition of matrix metalloproteinases (MMP)7 and MMP9. Oncogene NOTCH1 was revealed to be a putative target of miR-139-5p, which was inversely correlated with miR-139-5p expression (r = -0.3862, P = 0.0002).Conclusions: miR-139-5p plays a pivotal role in colon cancer through inhibiting cell proliferation, metastasis, and promoting apoptosis and cell cycle arrest by targeting oncogenic NOTCH1. © 2014 Zhang et al.; licensee BioMed Central Ltd.-
dc.languageeng-
dc.relation.ispartofMolecular Cancer-
dc.subjectColorectal cancer-
dc.subjectMiR-139-5p-
dc.subjectNOTCH1-
dc.subjectTumor suppressor-
dc.titleMicroRNA-139-5p exerts tumor suppressor function by targeting NOTCH1 in colorectal cancer-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1186/1476-4598-13-124-
dc.identifier.pmid24885920-
dc.identifier.scopuseid_2-s2.0-84904720607-
dc.identifier.volume13-
dc.identifier.issue1-
dc.identifier.spagearticle no. 124-
dc.identifier.epagearticle no. 124-
dc.identifier.eissn1476-4598-
dc.identifier.isiWOS:000338255100001-

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