miR-135a Targets SMAD2 to Promote Osteosarcoma Proliferation and Migration

Abstract

Osteosarcoma (OS) is an aggressive malignant neoplasm that commonly occurs in adults and adolescents. The objectives of this work were to verify the role of microRNA- (miR-) 135a in OS and determine whether it can regulate the growth and cellular migration of OS by targeting mothers against decapentaplegic homolog 2 (SMAD2). miR-135a and SMAD2 mRNA expression levels were measured using reverse transcription-quantitative PCR (RT-qPCR). Proliferation and migration of cells were studied using the Cell Counting Kit-8, EdU staining, and transwell invasion experiment. Additionally, a dual-luciferase reporter experiment was used to investigate the possible relationship between miR-135a and SMAD2’s 3 ′ -UTR. Immunohistochemistry was utilized to examine the expressions of SMAD2 and Ki67 in mouse tumor tissues to determine the influence of miR-135a on cancer progression in vivo. miR-135a was shown to be elevated in OS tissue samples as well as five cell lines. High expression levels of miR-135a were correlated with poor prognosis of OS patients. Cellular proliferation and migration were promoted by the upregulation of miR-135a with miR mimics; however, this effect was inhibited by SMAD2 overexpression. miR-135a was also shown to directly target the 3 ′ -UTR of SMAD2. Animal experiments also demonstrated that miR-135a downregulation had an inhibitory effect on tumor growth in vivo. High expression levels of miR-135a promoted transplanted tumor development in vivo and the proliferation and migration of OS cells by targeting SMAD2. In summary, miR-135a may be a prospective therapeutic target for OS in the future.

Tandem mass tag (TMT) quantitative protein analysis‐based proteomics and parallel reaction monitoring (PRM) validation revealed that MST4 accelerates osteosarcoma proliferation by increasing MRC2 activity

“…IHC analysis showed that the tumor tissues in the MST4 overexpression group contained large numbers of both MST4‐ and Ki67‐positive cells. These results suggest that MST4 can promote OS proliferation in vivo 22 . Taken together, our findings suggest that MST4 has potent protumor proliferative activity in OS both in vitro and in vivo and may be of clinical value in the treatment of patients with OS.…”

“…These results suggest that MST4 can promote OS proliferation in vivo. 22 Taken together, our findings suggest that MST4 has potent protumor proliferative activity in OS both in vitro and in vivo and may be of clinical value in the treatment of patients with OS.…”

The Role MicroRNA-135a in Suppressing Tumor Growth in Kidney Cancer Through the Regulation of Phosphoprotein Phosphatase2A and the Activation of the AKT and ERK1/2 Signaling Pathways

“…Several studies have explored the expression of miR-135a in KC and have found its expression to be lower in KC than in normal tissues (14). Furthermore, miR-135a has been found to have varying expression and functions among different types of tumors, indicating its significant role (25)(26)(27)(28).…”