miR-193b promotes cell proliferation by targeting Smad3 in human glioma.
Studies have shown that several miRNAs play important roles in regulating a variety of cellular processes in gliomas. In these reports, upregulation of miR-193b has been found to be associated with a poor prognosis for glioma, but its functional mechanism in glioma remains unclear. This study investigates the roles of miR-193b in glioma tumor growth. We first showed that the expression of miR-193b was elevated in both glioma samples and glioma cells. Furthermore, downregulation of miR-193b by inhibitors was statistically correlated with a decrease in cell growth and a restored G1 accumulation. Luciferase assay and Western blot analysis revealed that Smad3 is a direct target of miR-193b. To prove that miR-193b regulated cell growth through the transforming growth factor-β (TGF-β) pathway in glioma cells by regulating Smad3, we tested endogenous targets of the TGF-β pathway by measuring the accumulation of p21 mRNAs after downregulation of miR-193b. The results confirmed that induction of p21 was promoted by miR-193b inhibitors in glioma cells, although this induction disappeared when Smad3 was knocked down with siRNA. Moreover, downregulation of Smad3 mitigates the miR-193b suppression of glioma proliferation. In conclusion, these results suggest that miR-193b regulated cell growth in glioma through the TGF-β pathway by regulating Smad3. Thus, our study indicates that miR-193b promotes cell proliferation by targeting Smad3 in human glioma, which may serve as a potentially useful target for development of miRNA-based therapies in the future.
Department of Neurosurgery, General Hospital of Jinan Military Command of Chinese PLA, Jinan, Shandong, People's Republic of China.
Qisheng
Q
Zhong
Tongli
T
Wang
Peigang
P
Lu
Rongwei
R
Zhang
Jianan
J
Zou
Shaoji
S
Yuan
D000328:Adult; D001932:Brain Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000502:physiology*; D005910:Glioma / Q000473:pathology*; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009841:Oligonucleotides / Q000235:genetics / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000378:metabolism / Q000494:pharmacology; D012844:Sincalide / Q000494:pharmacology; D051900:Smad3 Protein / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014407:Tumor Cells, Cultured; D055815:Young Adult
C546818:MIRN193 microRNA, human; D035683:MicroRNAs; D009841:Oligonucleotides; D034741:RNA, Small Interfering; D051900:Smad3 Protein; D016212:Transforming Growth Factor beta; D012844:Sincalide
Smad3; cell proliferation; glioma; miR-193b; p21