title: MicroRNA-16 inhibits the proliferation, migration and invasion of glioma cells by targeting Sal-like protein 4.
abstract: MicroRNAs (miRNAs or miRs), a class of non-coding RNAs 18-25 nucleotides in length, act as key regulators in the development and malignant progression of various human cancers by modulating the expression of their target genes. Recently, miR‑16 has been demonstrated to be play a role in glioma. However, the regulatory mechanisms of miR‑16 in glioma growth and metastasis remain largely unclear. In the present study, qRT-PCR revealed that miR‑16 was significantly downregulated in 23 glioma tissue specimens compared to 7 normal brain tissue specimens. Moreover, its levels were markedly lower in the glioma samples at stages T2-T4 compared to those at stage T1. The overexpression of miR-16 significantly suppressed the proliferation, migration and invasion of U251 and U87 glioma cells. Luciferase reporter assay identified Sal-like protein 4 (SALL4) as a target gene of miR‑16, and its protein levels were found to be decreased in miR‑16-overexpressing U251 and U87 cells. Furthermore, the overexpression of SALL4 significantly reversed the suppressive effects of miR‑16 on the proliferation, migration and invasion of U251 and U87 cells, suggesting that miR‑16 playsa tumor suppressor role in glioma by inhibiting cell proliferation and invasion through the targeting of SALL4. Finally, we found that SALL4 was significantly upregulated in glioma tissues compared to normal brain tissues, and its levels were markedly higher in the glioma tissues at stages T2-T4 compared to those at stage T1. In addition, the expression levels of SALL4 inversely correlated with the miR‑16 levels in glioma tissues, suggesting that the downregulation of miR‑16 contributes to the upregulation of SALL4 in glioma. On the whole, the findings of this study indicate a role for the miR‑16/SALL4 axis in glioma. Our data may also provide a potential therapeutic target for the treatment of glioma.
authors.affiliation: Department of Neurosurgery, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Rehabilitation, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Radiology, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Chao
authors.initials: C
authors.lastname: Hu
authors.affiliation: Department of Neurosurgery, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Yugang
authors.initials: Y
authors.lastname: Jiang
mesh_terms: D020413:3' Untranslated Regions; D001665:Binding Sites; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D034622:RNA Interference; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; C505362:MIRN16 microRNA, human; D035683:MicroRNAs; C472575:SALL4 protein, human; D014157:Transcription Factors