Regulatory mechanism of microRNA‑128 in osteosarcoma tumorigenesis and evolution through targeting SASH1

Li,Zi; Ni,Jiangdong; Song,Deye; Ding,Muliang

doi:10.3892/ol.2018.8397

Regulatory mechanism of microRNA‑128 in osteosarcoma tumorigenesis and evolution through targeting SASH1

Authors:
- Zi Li
- Jiangdong Ni
- Deye Song
- Muliang Ding
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Affiliations: Department of Orthopedics, The Second Hospital of Xiangya Medical College of Central South University, Changsha, Hunan 410011, P.R. China
Published online on: March 30, 2018 https://doi.org/10.3892/ol.2018.8397
Pages: 8687-8694

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Abstract

Osteosarcoma, which commonly occurs in young individuals, is a type of malignant tumor of growing bones. MicroRNAs (miRNAs) have been found to be involved in various cancer‑related processes. In the present study, it was reported that miRNA‑128 (miR‑128) was overexpressed in pathological tissues from patients with osteosarcoma. The present study investigated the possible regulatory mechanism of miR‑128 on the progression of osteosarcoma and offered a foundation for clinical therapeutics in osteosarcoma. First, the expressions levels of miR‑128 and its target gene, SAM and SH3 domain‑containing 1 (SASH1), were measured in tissues from patients with osteosarcoma, and their correlation with osteosarcoma in terms of the pathological level were examined. The effects of miR‑128 on osteosarcoma cell proliferation and apoptosis were examined, and its regulation of the expression levels of SASH1 and associated proteins was analyzed. Subsequently, the association between SASH1 and miR‑128 was evaluated using a dual luciferase gene reporter assay. Finally, an in vivo xenograft tumor mouse model of osteosarcoma was established to confirm the in vitro results. The results demonstrated a higher expression of miR‑128 in pathological tissues, compared with that in normal tissues. From examining the patient osteosarcoma tissues, marked correlations were found between the expression of miR‑128 and that of SASH1, particularly with tumor size, invasion depth, lymph node metastasis, and tumor‑node‑metastasis stage. Compared with the negative control group and blank control group, the results showed that the inhibition of miR‑128 led to a lower cell proliferation rate and higher apoptotic rate in MG‑63 cells (P<0.05). Additionally, the expression of B‑cell lymphoma 2 (Bcl‑2) was downregulated in the miR‑128‑inhibited group, compared with that in the control group, whereas the expression levels of SASH1, Bcl‑2‑associated X protein and caspase‑3 were upregulated in the group with miR‑128 inhibition (P<0.05). SASH1 was confirmed as a direct target of miR‑128 using a dual luciferase gene reporter assay. Finally, the downregulation of miR‑128 was found to induce tumor suppressive effects on xenograft tumor models of osteosarcoma in mice in vivo. The results of the present study suggested that miR‑128 may regulate the tumorigenesis and evolution of osteosarcoma through targeting SASH1.

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