Down‐regulation of long non‐coding RNA MALAT RNA MALAT 1 by RNA RNA interference inhibits proliferation and induces apoptosis in multiple myeloma

摘要

Summary 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 ( MALAT 1), 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 MALAT 1 in MM remains unknown. In the present study, by transfecting MM cells with MALAT 1‐specific short hairpin RNA (sh RNA ) expression plasmids, the role of MALAT 1 in the proliferation and apoptosis of MM cells was investigated in vitro, and the tumorigenicity of MALAT 1 ‐silenced cells was evaluated in vivo. MALAT 1 was found to be highly expressed in RPMI 8226 and U266 cells. Down‐regulation of MALAT 1 via RNA interference significantly inhibited the proliferation of MM cells through cell cycle arrest at G1 phase. Moreover, knockdown of MALAT 1 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 MALAT 1 by intratumoral injection of MALAT 1 sh RNA attenuated the tumour growth in mice bearing myeloma xenograft and led to massive apoptosis in the xenograft tumour. Therefore, MALAT 1 may serve as a promising target in the genetic therapeutic strategy for MM treatment.