Down-regulation of long non-coding RNA MALAT1 by RNA interference inhibits proliferation and induces apoptosis in multiple myeloma.

Abstract

Multiple myeloma (MM) is a neoplastic plasma-cell disorder characterized by abnormal proliferation of monoclonal plasma cells in the bone marrow. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), an evolutionarily highly conserved long non-coding RNA was originally identified in metastatic non-small cell lung cancer and has been reported to be up-regulated in many other cancers. However, the function of MALAT1 in MM remains unknown. In the present study, by transfecting MM cells with MALAT1-specific short hairpin RNA (shRNA) expression plasmids, the role of MALAT1 in the proliferation and apoptosis of MM cells was investigated in vitro, and the tumorigenicity of MALAT1-silenced cells was evaluated in vivo. MALAT1 was found to be highly expressed in RPMI8226 and U266 cells. Down-regulation of MALAT1 via RNA interference significantly inhibited the proliferation of MM cells through cell cycle arrest at G1 phase. Moreover, knockdown of MALAT1 induced apoptosis, which was closely associated with the activation of caspase-3/-9, down-regulation of Bcl-2 and up-regulation of Bax. In addition, silencing of MALAT1 by intratumoral injection of MALAT1 shRNA attenuated the tumour growth in mice bearing myeloma xenograft and led to massive apoptosis in the xenograft tumour. Therefore, MALAT1 may serve as a promising target in the genetic therapeutic strategy for MM treatment.