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SMAD6, positively regulated by the DNM3OS-miR-134-5p axis, confers promoting effects to cell proliferation, migration and EMT process in retinoblastoma.


ABSTRACT: Background:Retinoblastoma (RB) is acknowledged to be the commonest intraocular malignancy in infants and children and the outcome of RB patients is unfavorable due to limited early diagnosis and effective therapy. SMAD family member 6 (SMAD6) has been reported in the initiation and progression of human cancers by acting as a biological participant. However, the role of SMAD6 in RB has not been illustrated yet. Methods:The expression of SMAD6 mRNA, miR-134-5p and DNM3OS was measured by RT-qPCR. SMAD6 protein levels were measured by western blot. The effects of SMAD6 depletion on RB cells were analyzed using CCK-8 and transwell assays. The key proteins related to epithelial-mesenchymal transition (EMT) was determined by western blot. The localization of DNM3OS was detected by nuclear/cytoplasmic assay. In addition, the direct interaction between miR-134-5p and SMAD6 or DNM3OS was confirmed with the application of dual-luciferase reporter assay. Results:SMAD6 was upregulated in RB tissue samples and cell lines, and silencing SMAD6 suppressed cell proliferation, migration and EMT in RB. Mechanically, SMAD6 was positively regulated by lncRNA DNM3OS through competitively interacting with miR-134-5p. DNM3OS contributed to RB progression by SMAD6-mediated manner. Conclusions:This research unmasked a novel DNM3OS/miR-134-5p/SMAD6 pathway in RB, which might make contribution to treatment of RB.

SUBMITTER: Wang H 

PROVIDER: S-EPMC6977187 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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SMAD6, positively regulated by the DNM3OS-miR-134-5p axis, confers promoting effects to cell proliferation, migration and EMT process in retinoblastoma.

Wang Hui H   Ji Xiang X  

Cancer cell international 20200122


<h4>Background</h4>Retinoblastoma (RB) is acknowledged to be the commonest intraocular malignancy in infants and children and the outcome of RB patients is unfavorable due to limited early diagnosis and effective therapy. SMAD family member 6 (SMAD6) has been reported in the initiation and progression of human cancers by acting as a biological participant. However, the role of SMAD6 in RB has not been illustrated yet.<h4>Methods</h4>The expression of SMAD6 mRNA, miR-134-5p and DNM3OS was measure  ...[more]

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