P16INK4a inhibits the proliferation of osteosarcoma cells through regulating the miR-146b-5p/TRAF6 pathway. Issue 2 (1st February 2019)

• Record Type: Journal Article
• Authors: Jiang, Mingwei; Lu, Wenjia; Ding, Xiaomin; Liu, Xiaodong; Guo, Zhen; Wu, Xu
• Is Part Of: Bioscience reports. Volume 39:Issue 2(2019)
• Publication Date: 2019-02-01
• Subjects: miR-146b-5p -- Osteosarcoma Cells -- p16INK4a -- tumor suppressors; Molecular biology -- Periodicals; Cytology -- Periodicals; 572.8
• DOI: 10.1042/BSR20181268
• Languages: English
• ISSNs: 0144-8463

Abstract

Abstract : Down-regulation of p16INK4a and miR-146b-5p contributes to tumorigenesis in osteosarcoma (OS). However, the correlation between p16INK4a and miR-146b-5p in OS proliferation remains largely unknown. In the present study, we demonstrated that miR-146b-5p expression was positively correlated with p16INK4a in OS, but inversely correlated with TNF receptor associated factor 6 (TRAF6) expression. Overexpression of miR-146b-5p dramatically suppressed OS cell proliferation. Mechanistically, we validated TRAF6 as a direct functional target of miR-146b-5p and found that miR-146b-5p overexpression significantly decreased the level of phosphorylated PI3k and Akt, which are the pivotal downstream effectors of TRAF6. Moreover, TRAF6 expression was positively correlated with Ki-67 but inversely correlated with miR-146b-5p expression. In OS cells, silencing of TRAF6 mimicked the anti-tumor effects of miR-146b-5p. p16INK4a is an important tumor suppressor gene frequently down-regulated in OS. We found that this inhibitory effect is associated with the suppression of the miR-146b-5p, and is mediated via up-regulating TRAF6 expression. Our findings identified p16INK4a and miR-146b-5p as tumor suppressors, and suggested p16INK4a, miR-146b-5p and TRAF6 as potential therapeutic candidates for malignant OS.