title: Tumor suppressor miR-1 restrains epithelial-mesenchymal transition and metastasis of colorectal carcinoma via the MAPK and PI3K/AKT pathway.
abstract: Aberrant expression of miR-1 has been implicated in various cancers. However, the mechanisms underlying the role of miR-1 in CRC progression still have not been clarified clearly. Here, we showed the decreased expression of miR-1 in colorectal carcinoma (CRC) tissues and cell lines. Ectopic introduction of miR-1 suppressed cell proliferation and migration, whereas miR-1 inhibitor performed contrary functions in CRC cells. Stable overexpression of miR-1 was sufficient to inhibit tumor growth and homing capacity in vivo. Proteomic analysis revealed that miR-1 modulated the expression of key cellular molecules and involved in the MAPK and PI3K/AKT pathways by inhibiting phosphorylation of ERK and AKT. Meanwhile, miR-1 also reversed epithelial-mesenchymal transition (EMT), which played a pivotal role in the initiation of metastasis. Further studies found that miR-1 can target the 3' untranslated region (3'UTR) of LIM and SH3 protein 1 (LASP1) mRNA and suppress the expression of LASP1, identified as a CRC-associated protein. In contrast to the phenotypes induced by miR-1 restoration, LASP1-induced cell proliferation and migration partly rescued miR-1-mediated biological behaviors. Our results illustrated that miR-1 play a critical role in CRC progression, which suggests its potential role in the molecular therapy of cancer.
authors.forename: Lijun
authors.initials: L
authors.lastname: Xu
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhang
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.forename: Guanhua
authors.initials: G
authors.lastname: Zhang
authors.forename: Yanqing
authors.initials: Y
authors.lastname: Ding
authors.forename: Liang
authors.initials: L
authors.lastname: Zhao
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000201:enzymology / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D006801:Humans; D020935:MAP Kinase Signaling System; D035683:MicroRNAs / Q000502:physiology*; D009362:Neoplasm Metastasis; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*
chemical_list: C544547:MIRN1 microRNA, human; D035683:MicroRNAs; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt