title: Targeting Smad2 and Smad3 by miR-136 suppresses metastasis-associated traits of lung adenocarcinoma cells.
abstract: TGF-β/Smad signaling induces epithelial-mesenchymal transition (EMT) and tumor metastasis. As essential mediators in this pathway, Smad2 and Smad3 have been extensively studied and found to promote EMT and the subsequent mobility as well as invasiveness of lung cancer cells. In the present study, we determined that miR-136 directly targeted Smad2 and Smad3, leading to reduced migration and invasiveness of lung adenocarcinoma (ADC) cell lines, accompanied by increased epithelial markers as well as decreased mesenchymal markers. Moreover, ectopic expression of either Smad2 or Smad3 partially restored the malignant phenotype of ADC cells overexpressing miR-136. Taken together, our data demonstrate that miR-136 may play a tumor-suppressive role by repressing EMT and prometastatic traits via targeting Smad2 and Smad3. The potent antimetastasis property of miR-136 and its multitarget mechanism provide new insights in developing novel therapeutic approaches.
authors.affiliation: Key Laboratory of Tropical Disease Control (Sun Yat-Sen University), Ministry of Education, Guangzhou, Guangdong, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Yang
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.forename: Junchao
authors.initials: J
authors.lastname: Cai
authors.forename: Jueheng
authors.initials: J
authors.lastname: Wu
authors.forename: Hongyu
authors.initials: H
authors.lastname: Guan
authors.forename: Xun
authors.initials: X
authors.lastname: Zhu
authors.forename: Jie
authors.initials: J
authors.lastname: Yuan
authors.forename: Shengping
authors.initials: S
authors.lastname: Chen
authors.forename: Mengfeng
authors.initials: M
authors.lastname: Li
mesh_terms: D020413:3' Untranslated Regions; D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology*; D000077192:Adenocarcinoma of Lung; D001483:Base Sequence; D001665:Binding Sites; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology*; D035683:MicroRNAs / Q000737:chemistry / Q000235:genetics*; D009362:Neoplasm Metastasis; D034622:RNA Interference; D051899:Smad2 Protein / Q000737:chemistry / Q000235:genetics*; D051900:Smad3 Protein / Q000737:chemistry / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; C577037:MIRN136 microRNA, human; D035683:MicroRNAs; D051899:Smad2 Protein; D051900:Smad3 Protein