title: Downregulation of microRNA-21 expression restrains non-small cell lung cancer cell proliferation and migration through upregulation of programmed cell death 4.
abstract: Preliminary studies showed that miR-21 is overexpressed in some human cancers. However, the role of miR-21 in cancer is still unclear and even controversial. Our purpose was to investigate the biological effects of miR-21 on A549 non-small cell lung cancer (NSCLC) cells and the underlying mechanisms of those effects. The expression of miR-21 was quantified in serum samples from patients with NSCLC. A549 cells were transfected with miR-NC-sponge or miR-21-sponge only, or with miR-21-sponge plus PDCD4 small-interfering RNA (siRNA). The expression of miR-21 and PDCD4 mRNA in transfected cells was quantified by real-time polymerase chain reaction and the expression of PDCD4 protein by Western blot. Cell proliferation, apoptosis, migration, and invasion assays were performed to determine the biological effects of miR-21 expression and PDCD4 inhibition. miR-21 was overexpressed in serum from patients with NSCLC. Reduced miR-21 expression was observed following transfection with miR-21-sponge in A549 NSCLC cells. Co-transfection of miR-21-sponge with PDCD4 siRNA upregulated miR-21 expression in these cells. PDCD4 mRNA and protein levels were increased 2.14-fold and 2.16-fold, respectively, following inhibition of miR-21 expression. Inhibition of miR-21 expression following transfection of miR-21-sponge reduced cell proliferation, migration, and invasion of A549 cells. Depletion of PDCD4 by siRNA transfection reversed the reduction of cell proliferation, migration, and invasion induced by inhibition of miR-21 in A549 cells. It indicates that miR-21 is highly expressed in patients with NSCLC and inhibition of miR-21 expression reduces proliferation, migration, and invasion of A549 cells by upregulating PDCD4 expression. Modulation of miR-21 or PDCD4 expression may provide a potentially novel therapeutic approach for NSCLC.
authors.affiliation: Wenzhou Medical University School of Laboratory Medicine and Life Sciences, Wenzhou, Zhejiang, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Wenzhou Medical University School of Laboratory Medicine and Life Sciences, Wenzhou, Zhejiang, China.
authors.forename: H
authors.initials: H
authors.lastname: Meng
authors.affiliation: Wenzhou Medical University School of Laboratory Medicine and Life Sciences, Wenzhou, Zhejiang, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Peng
authors.affiliation: Wenzhou Medical University School of Laboratory Medicine and Life Sciences, Wenzhou, Zhejiang, China.
authors.forename: X
authors.initials: X
authors.lastname: Yang
authors.affiliation: Wenzhou Medical University School of Laboratory Medicine and Life Sciences, Wenzhou, Zhejiang, China.
authors.forename: R
authors.initials: R
authors.lastname: Gan
authors.affiliation: Wenzhou Medical University School of Laboratory Medicine and Life Sciences, Wenzhou, Zhejiang, China.
authors.forename: L
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Laboratory Medicine, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Chen
authors.affiliation: 1] Wenzhou Medical University School of Laboratory Medicine and Life Sciences, Wenzhou, Zhejiang, China [2] Key Laboratory of Laboratory Medicine, Ministry of Education, Wenzhou, Zhejiang, China [3] Zhejiang Provincial Key Laboratory of Medical Genetics, Wenzhou, Zhejiang, China.
authors.forename: J
authors.initials: J
authors.lastname: Lu
authors.affiliation: Department of Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, USA.
authors.forename: Q H
authors.initials: QH
authors.lastname: Meng
mesh_terms: D000368:Aged; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000235:genetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D034622:RNA Interference; D016601:RNA-Binding Proteins / Q000235:genetics*
chemical_list: D051017:Apoptosis Regulatory Proteins; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; C114487:PDCD4 protein, human; D016601:RNA-Binding Proteins