title: The heterochronic microRNA let-7 inhibits cell motility by regulating the genes in the actin cytoskeleton pathway in breast cancer.
abstract: The heterochronic gene let-7 serves as a tumor suppressor microRNA by targeting various oncogenic pathways in cancer cells. Considerable evidence indicates that reduced expression of let-7 might be associated with poor clinical outcome in patients with cancer. Here, we report that the expression levels of three let-7 family members, let-7a, let-7b, and let-7g, were significantly decreased in the patients with breast cancer with lymph node metastasis compared with those without lymph node metastasis. Enforced expression of let-7b significantly inhibits breast cancer cell motility and affects actin dynamics. Using bioinformatic and experimental approaches, four genes in the actin cytoskeleton pathway, including PAK1, DIAPH2, RDX, and ITGB8, were identified as let-7 direct targets. Blocking the expression of PAK1, DIAPH2, and RDX significantly inhibits breast cancer cell migration induced by let-7b repression. Our results indicate that reconstitution of let-7 expression in tumor cells could provide a novel therapeutic strategy for the treatment of metastatic disease.
authors: Center for Research on Reproduction and Women's Health, University of Pennsylvania, Philadelphia, PA, USA.
authors: Xiaowen
authors: X
authors: Hu
authors: Jinyi
authors: J
authors: Guo
authors: Lan
authors: L
authors: Zheng
authors: Chunsheng
authors: C
authors: Li
authors: Tim M
authors: TM
authors: Zheng
authors: Janos L
authors: JL
authors: Tanyi
authors: Shun
authors: S
authors: Liang
authors: Chiara
authors: C
authors: Benedetto
authors: Marco
authors: M
authors: Mitidieri
authors: Dionyssios
authors: D
authors: Katsaros
authors: Xia
authors: X
authors: Zhao
authors: Youcheng
authors: Y
authors: Zhang
authors: Qihong
authors: Q
authors: Huang
authors: Lin
authors: L
authors: Zhang
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002352:Carrier Proteins / Q000378:metabolism; D002465:Cell Movement / Q000235:genetics*; D003598:Cytoskeletal Proteins / Q000378:metabolism; D005260:Female; D000080865:Formins; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016023:Integrins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D053858:Metabolic Networks and Pathways / Q000235:genetics; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009362:Neoplasm Metastasis / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D015398:Signal Transduction; D054462:p21-Activated Kinases / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; C491462:DIAPH2 protein, human; D000080865:Formins; D016023:Integrins; D008565:Membrane Proteins; D035683:MicroRNAs; C487931:mirnlet7 microRNA, human; C071776:radixin; C515903:PAK1 protein, human; D054462:p21-Activated Kinases