Characterization of complete lncRNAs transcriptome reveals the functional and clinical impact of lncRNAs in multiple myeloma.
Characterization of complete lncRNAs transcriptome reveals the functional and clinical impact of lncRNAs in multiple myeloma.
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DOI：
10.1038/s41375-021-01147-y
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发表时间：
2021-05
期刊：
影响因子：
11.4
通讯作者：
Agirre X
中科院分区：
文献类型：
--
作者：
Carrasco-Leon A;Ezponda T;Meydan C;Valcárcel LV;Ordoñez R;Kulis M;Garate L;Miranda E;Segura V;Guruceaga E;Vilas-Zornoza A;Alignani D;Pascual M;Amundarain A;Castro-Labrador L;Martín-Uriz PS;El-Omri H;Taha RY;Calasanz MJ;Planes FJ;Paiva B;Mason CE;San Miguel JF;Martin-Subero JI;Melnick A;Prosper F;Agirre X
Multiple myeloma (MM) is an incurable disease, whose clinical heterogeneity makes its management challenging, highlighting the need for biological features to guide improved therapies. Deregulation of specific long non-coding RNAs (lncRNAs) has been shown in MM, nevertheless, the complete lncRNA transcriptome has not yet been elucidated. In this work, we identified 40,511 novel lncRNAs in MM samples. lncRNAs accounted for 82% of the MM transcriptome and were more heterogeneously expressed than coding genes. A total of 10,351 overexpressed and 9,535 downregulated lncRNAs were identified in MM patients when compared with normal bone-marrow plasma cells. Transcriptional dynamics study of lncRNAs in the context of normal B-cell maturation revealed 989 lncRNAs with exclusive expression in MM, among which 89 showed de novo epigenomic activation. Knockdown studies on one of these lncRNAs, SMILO (specific myeloma intergenic long non-coding RNA), resulted in reduced proliferation and induction of apoptosis of MM cells, and activation of the interferon pathway. We also showed that the expression of lncRNAs, together with clinical and genetic risk alterations, stratified MM patients into several progression-free survival and overall survival groups. In summary, our global analysis of the lncRNAs transcriptome reveals the presence of specific lncRNAs associated with the biological and clinical behavior of the disease.
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影响因子：
64.8
作者：
Ernst, Jason;Kheradpour, Pouya;Mikkelsen, Tarjei S.;Shoresh, Noam;Ward, Lucas D.;Epstein, Charles B.;Zhang, Xiaolan;Wang, Li;Issner, Robbyn;Coyne, Michael;Ku, Manching;Durham, Timothy;Kellis, Manolis;Bernstein, Bradley E.
通讯作者：
Bernstein, Bradley E.
表观遗传学在多发性骨髓瘤生物学中的作用。
影响因子：
12.8
作者：
Dimopoulos, K.;Gimsing, P.;Gronbaek, K.
通讯作者：
Gronbaek, K.
影响因子：
2.4
作者：
Hauptman N;Glavac D
通讯作者：
Glavac D
影响因子：
11.4
作者：
Beck, D.;Thoms, J. A. I.;Pimanda, J. E.
通讯作者：
Pimanda, J. E.
DOI：
10.1126/science.aad5497
发表时间：
2016-03-04
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Chuong EB;Elde NC;Feschotte C
通讯作者：
Feschotte C