Long noncoding RNA MALAT1 promotes cell proliferation through suppressing miR-205 and promoting SMAD4 expression in osteosarcoma

Abstract

Increasing evidences have indicated that long non-coding RNAs (lncRNAs) play an important role in multiply biological processes including cell development, differentiation, proliferation and invasion. The metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), is a highly conserved nuclear ncRNA and a key regulator of metastasis development in several cancers. However, its role in osteosarcoma progression is not well known. In this study, we sought to determine the clinical and bilogical role of MALAT1 in osteosarcoma progression. RT-qPCR analysis showed that MALAT1 expression was significantly increased in primary osteosarcoma tissues and cell lines. Kaplan-Meier analysis indicated that patients with high expression of MALAT1 was associated with poor overall survival compared with the low expressing patients. Furthermore, the gain and loss function assay showed that miR-205 was suppressed by MALAT1 in osteosarcoma and this interaction between miR-205 and MALAT1 has reciprocal effects. Cell viability assay showed that MALAT1 promoted MG-63 and SAOS-2 cell growth through suppressing miR-205. Subsequently, the downstream gene SMAD4 was identified as a direct functional target of miR-205, and miR-205 suppressed osteosarcoma cell growth through suppressing SMAD4. Finally, we demonstrated that MALAT1 promoted osteosarcoma progression via a miR-205-SMAD4 axis. In conclusion, we revealed that enhanced MALAT1 expression predicted unfavourable outcome in osteosarcoma and promoted cell proliferation through suppressing miR-205 and activating SMAD4 function. Thus, lncRNA MALAT1 may serve as a promising prognostic and therapeutic target for osteosarcoma patients.