Abstract

BACKGROUND: Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a functional long non-coding RNA involved in many biologic processes. The study was aimed to explore the functional roles of MALAT1 in osteosarcoma progression.

MATERIAL AND METHODS: A total of 76 osteosarcoma tissues and paired adjacent non-tumor tissues were collected from surgical resection. MALAT1, miRNAs, and genes mRNA expression levels were detected using quantitative real-time PCR (qRT-PCR). Protein expression level, cell proliferation, migration, and invasion were assessed using western blot, Cell Counting Kit-8 (CCK-8), wound-healing assay, and Matrigel invasion assay respectively. The target relationships among miRNAs, MALAT1, and mRNA were detected via dual-luciferase reporter assay.

RESULTS: We found that MALAT1 was frequently upregulated in osteosarcoma samples and cell lines and a high level of MALAT1 predicted poor overall survival in osteosarcoma patients. Knockdown of MALAT1 inhibited proliferation, migration, and invasion of osteosarcoma cells. Further study showed a positive correlation between MALAT1 and c-Met or SOX4 expression. Mechanistic investigations demonstrated that MALAT1, as a competing endogenous RNA (ceRNA), regulated osteosarcoma proliferation and metastasis through competitively binding to miR-34a/c-5p and miR-449a/b.

CONCLUSIONS: Taken together, our study illustrates a new regulatory mechanism for MALAT1 and may provide a novel therapeutic strategy for the treatment of osteosarcoma.

Keywords: Neoplasm Metastasis, Osteosarcoma, Adolescent, Bone Neoplasms, Child, Middle Aged, Neoplasm Invasiveness, RNA, Long Noncoding, RNA, Messenger, RNA, Small Interfering, Receptor Protein-Tyrosine Kinases, SOXC Transcription Factors, Up-Regulation