Todoerti Katia, Ronchetti Domenica, Puccio Noemi, Silvestris Ilaria, Favasuli Vanessa, Amodio Nicola, Gentile Massimo, Morabito Fortunato, Neri Antonino, Taiana Elisa
Department of Oncology and Hemato-Oncology, University of Milan, 20122 Milan, Italy.
Hematology, Fondazione Cà Granda IRCCS Policlinico, 20122 Milan, Italy.
Cancers (Basel). 2021 Nov 3;13(21):5518. doi: 10.3390/cancers13215518.
The biological impact of long non-coding RNAs (lncRNAs) in multiple myeloma (MM) is becoming an essential aspect of the investigation, which may contribute to understanding the disease's complex pathobiology, providing novel potential therapeutic targets. Herein, we investigated the expression pattern and the clinical relevance of the lncRNA MIAT in MM, taking advantage of the publicly available CoMMpass database. MIAT expression in MM is highly heterogeneous and significantly associated with specific molecular lesions frequently occurring in MM. Transcriptome analyses of MM PCs from patients included in the CoMMpass database indicated a potential involvement of MIAT in different signaling pathways and ribosome biogenesis and assembly. These findings suggest that MIAT deregulation may play a pathogenetic role in MM by affecting both proliferation pathways and, indirectly, the translational process. Although MIAT expression levels seem not to be significantly associated with clinical outcome in multivariate analyses, high MIAT expression levels are associated with bortezomib resistance, this suggesting that MIAT targeting could overcome drug resistance in MM. These findings strongly prompt for further studies investigating the significance of MIAT in MM.
长链非编码RNA（lncRNA）在多发性骨髓瘤（MM）中的生物学影响正成为研究的一个重要方面，这可能有助于理解该疾病复杂的病理生物学，提供新的潜在治疗靶点。在此，我们利用公开可用的CoMMpass数据库，研究了lncRNA MIAT在MM中的表达模式及其临床相关性。MM中MIAT的表达高度异质性，且与MM中频繁出现的特定分子病变显著相关。对CoMMpass数据库中患者的MM浆细胞进行转录组分析表明，MIAT可能参与不同的信号通路以及核糖体生物合成和组装。这些发现提示，MIAT失调可能通过影响增殖途径以及间接影响翻译过程，在MM的发病机制中发挥作用。尽管在多变量分析中，MIAT表达水平似乎与临床结局无显著相关性，但高MIAT表达水平与硼替佐米耐药相关，这表明靶向MIAT可能克服MM中的耐药性。这些发现强烈促使进一步研究MIAT在MM中的意义。
