Liu Hui, Wang Huihan, Wu Bin, Yao Kun, Liao Aijun, Miao Miao, Li Yang, Yang Wei
Department of Hematology, Affiliated Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, China.
Clin Exp Pharmacol Physiol. 2017 Oct;44(10):1032-1041. doi: 10.1111/1440-1681.12804. Epub 2017 Aug 24.
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.
多发性骨髓瘤（MM）是一种肿瘤性浆细胞疾病，其特征是骨髓中克隆性浆细胞异常增殖。转移相关的肺腺癌转录本1（MALAT1）是一种在进化上高度保守的长链非编码RNA，最初在转移性非小细胞肺癌中被鉴定出来，并且据报道在许多其他癌症中上调。然而，MALAT1在MM中的功能仍然未知。在本研究中，通过用MALAT1特异性短发夹RNA（shRNA）表达质粒转染MM细胞，在体外研究了MALAT1在MM细胞增殖和凋亡中的作用，并在体内评估了MALAT1沉默细胞的致瘤性。发现MALAT1在RPMI8226和U266细胞中高表达。通过RNA干扰下调MALAT1可通过使细胞周期停滞在G1期而显著抑制MM细胞的增殖。此外，敲低MALAT1诱导凋亡，这与caspase-3/-9的激活、Bcl-2的下调和Bax的上调密切相关。另外，通过瘤内注射MALAT1 shRNA沉默MALAT1可减弱携带骨髓瘤异种移植瘤小鼠的肿瘤生长，并导致异种移植瘤中大量凋亡。因此，MALAT1可能成为MM治疗基因治疗策略中有前景的靶点。
