The Downregulation of MiR-182 Is Associated with the Growth and Invasion of Osteosarcoma Cells through the Regulation of TIAM1 Expression

<div><p>Background</p><p>Osteosarcoma is the most common primary bone malignancy in children and young adults. Increasing results suggest that discovery of microRNAs (miRNAs) might provide a novel therapeutical target for osteosarcoma.</p><p>Methods</p><p>MiR-182 expression level in osteosarcoma cell lines and tissues were assayed by qRT-PCR. MiRNA mimics or inhibitor were transfected for up-regulation or down-regulation of miR-182 expression. Cell function was assayed by CCK8, migration assay and invasion assay. The target genes of miR-182 were predicated by bioinformatics algorithm (TargetScan Human).</p><p>Results</p><p>MiR-182 was down-regulated in osteosarcoma tissues and cell lines. Overexpression of miR-182 inhibited tumor growth, migration and invasion. Subsequent investigation revealed that TIAM1 was a direct and functional target of miR-182 in osteosarcoma cells. Overexpression of miR-182 impaired TIAM1-induced inhibition of proliferation and invasion in osteosarcoma cells.</p><p>Conclusions</p><p>Down-expression of miR-182 in osteosarcoma promoted tumor growth, migration and invasion by targeting TIAM1. MiR-182 might act as a tumor suppressor gene whose down-regulation contributes to the progression and metastasis of osteosarcoma, providing a potential therapy target for osteosarcoma patients.</p></div

Overexpression of miR-182 inhibited tumor growth.

<p>(A) The miR-182 expression level of the indicated cells was measured by qRT-PCR. The expression of miR-182 was normalized to U6 snRNA. (B) The expression level of miR-182 in the indicated cells was measured by qRT-PCR. The expression of miR-182 was normalized to U6 snRNA. (C) Cell proliferation of the indicated cells was analyzed using CCK-8 assay. (D) Inhibition of miR-182 promote the osteosarcoma cell proliferation. *p<0.05, ** p<0.01, and ***p<0.001.</p

Overexpression of miR-182 inhibited tumor invasion.

<p>(A) Wound-healing assay was employed to evaluate the migratory ability of MG-63 cells after treatment with miR-182 mimics, inhibitors or scramble or no transfection. Relative ratio of wound closure is shown on the right. (B) Invasion analysis were employed to evaluate the invasive ability of the MG-63 cells after treatment with miR-182 mimics, inhibitors or scramble or no transfection; the relative ratio of invasive cells per field is shown on the right, *p<0.05, ** p<0.01, and ***p<0.001.</p

miR-182 was down-regulated in osteosarcoma cell lines and tissues.

<p>(A) The expression levels of miR-182 were measured by qRT-PCR in osteosarcoma cell lines (U2OS, MG-63, SOSP-9607, and SAOS-2) and human normal osteoblastic cell line (hFOB). The expression of miR-182 was down-regulated in osteosarcoma cell lines. (B) Relative expression of miR-182 in 40 primary osteosarcoma tissues compared with their pair-matched nontumor tissues. Data are shown as log2 of relative ratio change of osteosarcoma tissues relative to normal tissues. (C) The expression of miR-182 in the human osteosarcoma tissues was lower than that in non-tumor adjacent tissues. (D) Loss of miR-182 levels in patients with osteosarcoma was associated with associated with considerably shortened disease-free survival. All data were normalized by U6 snRNA. ***p<0.001.</p

Restoration of miR-182 inhibits TIAM1-inducing osteosarcoma cell proliferation and invasion.

<p>(A) qRT-PCR analysis of TIAM1 expression in osteosarcoma cell lines (U2OS, MG-63, SOSP-9607, and SAOS-2) and human normal osteoblastic cell line (hFOB). The mRNA expression of TIAM1 was up-regulated in osteosarcoma cell lines. The expression of TIAM1 was normalized to GAPDH. (B) Western blot analysis of TIAM1 expression in osteosarcoma cell lines (U2OS, MG-63, SOSP-9607, and SAOS-2) and human normal osteoblastic cell line (hFOB). The protein expression of TIAM1 was up-regulated in osteosarcoma cell lines. GAPDH was also detected as a loading control. (C) The effects of pCDNA-TIAM1 on the expression of TIAM1 was detected by Western blotting. GAPDH was also detected as a loading control. (B) The cell growth in MG-63 co-transfected with either miR-182 mimic or scramble and 2.0 μg pCDNA-TIAM1 or pCDNA empty vector using CCK-8 proliferation assay. (C) The cell invasive in MG-63 co-transfected with either miR-182 mimic or scramble and 2.0 μg pCDNA-TIAM1 or pCDNA empty vector using invasion assay. *p<0.05, ** p<0.01, and ***p<0.001.</p

Structure and Electrochemical Properties of Bronze Phase Materials Containing Two Transition Metals

Bronze phase transition-metal oxides have recently attracted attention as high-rate lithium-ion battery anode materials. Their crystal structures are distinguished by large tunnels and an open framework, facilitating lithium-ion diffusion and high-rate charge–discharge properties. The presence of two transition metals also offers a route to achieve high energy density from multielectron redox. In this paper, we report the chemistry, structure, and electrochemical properties of two different bronze phase compositions having the same stoichiometry: W3Nb2O14 and Mo3Nb2O14. These materials provide insight into how the transition metals affect the electrochemical behavior and structural stability of bronze phase materials. Mo3Nb2O14 exhibits greater than 1 electron redox per transition metal leading to lithium capacities above 200 mAh g–1 at C/2 but is unable to maintain this high capacity at high rates due to incomplete Mo redox reactions. In contrast, W3Nb2O14 exhibits reversible redox reactions and retains its open structure on cycling. This study highlights the potential of bronze phase materials containing two transition metals to exhibit fast charging properties with a high energy density

Optimal Bandgap in a 2D Ruddlesden–Popper Perovskite Chalcogenide for Single-Junction Solar Cells

Optimal Bandgap in a 2D Ruddlesden–Popper Perovskite Chalcogenide for Single-Junction Solar Cell